Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in e...Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.展开更多
Objective:To explore the molecular mechanism of Xuanbai Chengqi Decoction(宣白承气汤)in the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology,and to verify by molecular docking technology.Me...Objective:To explore the molecular mechanism of Xuanbai Chengqi Decoction(宣白承气汤)in the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology,and to verify by molecular docking technology.Methods:The components and targets of Xuanbai Chengqi Decoction(宣白承气汤)were obtained by TCMSP,targets’information was corrected based on the databases such as UniP rot and DrugBank,and the software Cytoscape3.7.1 was adopted to construct TCM-Component-Target and Component-Target network.The main targets were mapped to the KEGG pathway and the GO biological process with the help of DAVID to further elucidate the potential relationship between the main targets and Xuanbai Chengqi Decoction(宣白承气汤)therapy for COVID-19.In the end,the Swiss Dock platform was adopted for the molecular docking verification of key components and targets.Results:The Component-Target network consists of 35 components and 106 corresponding targets,the main targets include COX-2,NCOA2,PTGS1,HSP90 AB1,PRKACA and PGR,etc.There are 561 GO entries of target mapping(P 0.05),including 155 entries for Biological Processes(BP),147 entries for Cell Composition(CC),and 259 entries for Molecular Function(MF).There are 38 KEGG mapping pathways(P 0.05),including many aspects of infectious disease,immune system and endocrine system,as well as Calcium signaling pathway,VEGF signaling pathway,PI3K-Akt signaling pathway and other processes.Conclusion:The result of molecular docking shows that the affinity of the key components such as beta-sitosterol and stigmasterol are similar to recommended medications for COVID-19.Its effect in the treatment of middle stage of COVID-19 may be related to the blocking of the binding of COVID-19 virus and ACE2,antivirus,and relieving inflammatory storm.展开更多
The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury(AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human re...The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury(AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells(KPTECs) in 2 D and 3 D culture systems using conditional reprogramming(CR) and organoids techniques.These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters(SLC34 A3 and cubilin). They also expressed angiotensin-converting enzyme 2(ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34 A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3 D organoids culture compared to that in 2 D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike(S) protein was able to enter CR cells with luciferase reporter. This integrated 2 D CR and 3 D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation.展开更多
Global prevalence of coronavirus disease 2019(COVID-19)calls for an urgent development of anti-viral regime.Compared with the development of new drugs,drug repurposing can significantly reduce the cost,time,and safety...Global prevalence of coronavirus disease 2019(COVID-19)calls for an urgent development of anti-viral regime.Compared with the development of new drugs,drug repurposing can significantly reduce the cost,time,and safety risks.Given the fact that coronavirus harnesses spike protein to invade host cells through angiotensinconverting enzyme 2(ACE2),hence we see if any previous anti-virtual compounds can block spike-ACE2 interaction and inhibit the virus entry.The results of molecular docking and molecular dynamic simulations revealed that remdesivir exhibits better than expected anti-viral invasion potential against COVID-19 among the three types of compounds including remdesivir,tenofovir and lopinavir.In addition,a positive correlation between the surface area occupied by remdesivir and anti-viral invasion potential was also found.As such,the structure of remdesivir was modified by linking an N-benzyl substituted diamidine derivative to its hydroxyl group through an ester bond.It was found that this compound has a higher anti-viral invasion potential and greater specificity.展开更多
Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)are at increased risk of acute lung injury.However,it is still not clear wheth...Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)are at increased risk of acute lung injury.However,it is still not clear whether this increased risk is related to the usage of renin-angiotensin system(RAS)blockers.We collected medical records of coronavirus disease 2019(COVID-19)patients from the First Affiliated Hospital,Zhejiang University School of Medicine(Hangzhou,China),and evaluated the potential impact of an angiotensin II receptor blocker(ARB)on the clinical outcomes of COVID-19 patients with hypertension.A total of 30 hypertensive COVID-19 patients were enrolled,of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received.Compared with the non-ARB group,patients in the ARB group had a lower proportion of severe cases and intensive care unit(ICU)admission as well as shortened length of hospital stay,and manifested favorable results in most of the laboratory testing.Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course.No significant difference in the time of seroconversion or antibody levels was observed between the two groups.The median levels of soluble angiotensin-converting enzyme 2(sACE2)in serum and urine samples were similar in both groups,and there were no significant correlations between serum sACE2 and biomarkers of disease severity.Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport,bicarbonate transport,and blood coagulation.Our results suggest that ARB usage is not associated with aggravation of COVID-19.These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.展开更多
Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate t...Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.展开更多
The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(A...The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.展开更多
目的探讨替米沙坦干预对自发性高血压大鼠(SHR)血管组织血管紧张素转换酶2(ACE2)基因表达、一氧化氮(NO)及氧化应激水平的影响。方法选取10周龄SHR及其同源对照WKY大鼠,分别给予替米沙坦(5、10 mg.kg-1.d-1)或安慰剂,为期10周。采用West...目的探讨替米沙坦干预对自发性高血压大鼠(SHR)血管组织血管紧张素转换酶2(ACE2)基因表达、一氧化氮(NO)及氧化应激水平的影响。方法选取10周龄SHR及其同源对照WKY大鼠,分别给予替米沙坦(5、10 mg.kg-1.d-1)或安慰剂,为期10周。采用Western blot检测治疗后大鼠主动脉组织中ACE2蛋白及内皮型NO合酶(eNOS)磷酸化水平。分别采用硝酸还原酶比色法与硫代巴比妥酸比色法测定大鼠主动脉组织中NO和丙二醛(MDA)含量。结果与WKY对照组相比,SHR大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平明显降低(ACE2:0.39±0.05vs 1.00±0.06;p-eNOS:0.43±0.06 vs 1.00±0.04;P值均<0.01),伴NO水平下调及MDA含量增加(NO mmol.g-1protein:11.5±2.1 vs 27.8±4.9;MDA nmol.g-1 protein:393.9±17.9 vs 186.3±14.5;P值均<0.01),而经替米沙坦治疗后SHR低、高剂量治疗组大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平增加(ACE2:0.62±0.06,0.65±0.07 vs 0.39±0.05;p-eNOS:0.68±0.07,0.71±0.06 vs0.43±0.06;P值均<0.05),伴NO水平升高(19.2±3.3,23.9±3.2 vs 11.5±2.1 mmol.g-1protein;P值均<0.05)与MDA含量下调(271.9±16.1,249.2±19.6 vs 393.9±17.9nmol.g-1protein;P值均<0.05)。结论长期替米沙坦治疗通过提升高血压大鼠血管ACE2表达及eNOS磷酸化水平,可促使血管NO生成及氧化应激水平改善,提示替米沙坦对高血压具有一定的血管保护功效。展开更多
基金supported by the National Science and Technology Major Project(2018ZX10711-001)(2017YFA0205100)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.
基金Supported by Wannan Medical College Youth Fund,No.WK201804。
文摘Objective:To explore the molecular mechanism of Xuanbai Chengqi Decoction(宣白承气汤)in the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology,and to verify by molecular docking technology.Methods:The components and targets of Xuanbai Chengqi Decoction(宣白承气汤)were obtained by TCMSP,targets’information was corrected based on the databases such as UniP rot and DrugBank,and the software Cytoscape3.7.1 was adopted to construct TCM-Component-Target and Component-Target network.The main targets were mapped to the KEGG pathway and the GO biological process with the help of DAVID to further elucidate the potential relationship between the main targets and Xuanbai Chengqi Decoction(宣白承气汤)therapy for COVID-19.In the end,the Swiss Dock platform was adopted for the molecular docking verification of key components and targets.Results:The Component-Target network consists of 35 components and 106 corresponding targets,the main targets include COX-2,NCOA2,PTGS1,HSP90 AB1,PRKACA and PGR,etc.There are 561 GO entries of target mapping(P 0.05),including 155 entries for Biological Processes(BP),147 entries for Cell Composition(CC),and 259 entries for Molecular Function(MF).There are 38 KEGG mapping pathways(P 0.05),including many aspects of infectious disease,immune system and endocrine system,as well as Calcium signaling pathway,VEGF signaling pathway,PI3K-Akt signaling pathway and other processes.Conclusion:The result of molecular docking shows that the affinity of the key components such as beta-sitosterol and stigmasterol are similar to recommended medications for COVID-19.Its effect in the treatment of middle stage of COVID-19 may be related to the blocking of the binding of COVID-19 virus and ACE2,antivirus,and relieving inflammatory storm.
基金supported by the National Natural Science Foundation of China (81571396 and 81771528)Science, Technology and Innovation Commission of Shenzhen Municipality (JCYJ20170411090932146, JCYJ20170818110544730)。
文摘The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury(AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells(KPTECs) in 2 D and 3 D culture systems using conditional reprogramming(CR) and organoids techniques.These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters(SLC34 A3 and cubilin). They also expressed angiotensin-converting enzyme 2(ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34 A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3 D organoids culture compared to that in 2 D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike(S) protein was able to enter CR cells with luciferase reporter. This integrated 2 D CR and 3 D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation.
文摘Global prevalence of coronavirus disease 2019(COVID-19)calls for an urgent development of anti-viral regime.Compared with the development of new drugs,drug repurposing can significantly reduce the cost,time,and safety risks.Given the fact that coronavirus harnesses spike protein to invade host cells through angiotensinconverting enzyme 2(ACE2),hence we see if any previous anti-virtual compounds can block spike-ACE2 interaction and inhibit the virus entry.The results of molecular docking and molecular dynamic simulations revealed that remdesivir exhibits better than expected anti-viral invasion potential against COVID-19 among the three types of compounds including remdesivir,tenofovir and lopinavir.In addition,a positive correlation between the surface area occupied by remdesivir and anti-viral invasion potential was also found.As such,the structure of remdesivir was modified by linking an N-benzyl substituted diamidine derivative to its hydroxyl group through an ester bond.It was found that this compound has a higher anti-viral invasion potential and greater specificity.
基金supported by the Department of Education of Zhejiang Province(No.Y202043382)the National Natural Science Foundation of China(Nos.82072377 and 81971919)。
文摘Epidemiological evidence suggests that patients with hypertension infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)are at increased risk of acute lung injury.However,it is still not clear whether this increased risk is related to the usage of renin-angiotensin system(RAS)blockers.We collected medical records of coronavirus disease 2019(COVID-19)patients from the First Affiliated Hospital,Zhejiang University School of Medicine(Hangzhou,China),and evaluated the potential impact of an angiotensin II receptor blocker(ARB)on the clinical outcomes of COVID-19 patients with hypertension.A total of 30 hypertensive COVID-19 patients were enrolled,of which 17 were classified as non-ARB group and the remaining 13 as ARB group based on the antihypertensive therapies they received.Compared with the non-ARB group,patients in the ARB group had a lower proportion of severe cases and intensive care unit(ICU)admission as well as shortened length of hospital stay,and manifested favorable results in most of the laboratory testing.Viral loads in the ARB group were lower than those in the non-ARB group throughout the disease course.No significant difference in the time of seroconversion or antibody levels was observed between the two groups.The median levels of soluble angiotensin-converting enzyme 2(sACE2)in serum and urine samples were similar in both groups,and there were no significant correlations between serum sACE2 and biomarkers of disease severity.Transcriptional analysis showed 125 differentially expressed genes which mainly were enriched in oxygen transport,bicarbonate transport,and blood coagulation.Our results suggest that ARB usage is not associated with aggravation of COVID-19.These findings support the maintenance of ARB treatment in hypertensive patients diagnosed with COVID-19.
基金This work was supported by National 13th Five-Year Science and Technology Plan Major Projects of China(2017ZX10203205 to G.Chen)National Key R&D Plan(2017YFA0104304 to Y.Yang)+6 种基金Na-tional Natural Science Foundation of China(81770648 to Y.Yang)Guangdong Natural Science Foundation(2015A030312013 to Y.Yang)Science and Technology Program of Guangdong Province(2017B020209004 and 2017B030314027 to G.Chen)Science and Technology Program of Guangzhou city(201508020262 to Y.Yang)Collaborative Innovation Major Special Projects of Guangzhou City(201604020007 to F.Yang)Project funded by China Postdoctoral Science Foundation(2019M653904XB to F.Yang)Natural Science Foundation of Xinjiang Uyghur Autonomous Region(2020D01C006 to F.Yang).
文摘Background and aim:Coronavirus disease 2019(COVID-19)is a life-threatening disease that predomi-nantly causes respiratory failure.The impact of COVID-19 on other organs remains elusive.Herein,we aimed to investigate the effects of COVID-19 on the hepatobiliary system.Methods:In the current study,we obtained the clinical records and laboratory results from 66 laboratory-confirmed patients with COVID-19 at the Wuhan Tongji Hospital between 10 February 2020 and 28 February 2020.The detailed clinical features and laboratory findings were collected for analysis.Bioinformatics analysis was conducted to evaluate the correlation between gamma-glutamyl transferase(GGT)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entry receptor angiotensin-converting enzyme 2(ACE2).Results:In this cohort,30(51.7%)patients had abnormal liver function on admission,which was asso-ciated with disease severity and enriched in the male and diabetic patients.The elevated levels of direct bilirubin(P¼0.029)and GGT(P¼0.004)were common in patients with severe pneumonia when compared with those with mild pneumonia.In addition,elevated levels of GGT(P¼0.003)and aspartate aminotransferase(AST)(P¼0.007)were positively associated with longer hospital stay.The expression of ACE2 was closely associated with GGT in various human tissues because they shared the common transcriptional regulator hepatic nuclear factor-1 b(HNF1B).Conclusions:Increased GGT levels were common in severe cases and elevated GGT levels were positively associated with prolonged hospital stay and disease severity.Due to the consistent expression with ACE2,GGT is a potent biomarker indicating the susceptibility of SARS-CoV-2 infection.
基金supported by the National Natural Science Foundation of China(81871662,82150201)Xi’an Jiaotong University Fund(xzy012019066 and xzy032020037)Xi’an Jiaotong University Health Science Center-Qinnong Bank Fund(QNXJTU-04&QNXJTU-07)。
文摘The recent COVID-19 pandemic poses a global health emergency.Cellular entry of the causative agent SARS-CoV-2 is mediated by its spike protein interacting with cellular receptor-human angiotensin converting enzyme 2(ACE2).Here,by using lentivirus based pseudotypes bearing spike protein,we demonstrated that entry of SARS-CoV-2 into host cells was dependent on clathrin-mediated endocytosis,and phosphoinositides played essential roles during this process.In addition,we showed that the intracellular domain and the catalytic activity of ACE2 were not required for efficient virus entry.Finally,we showed that the current predominant Delta variant,although with high infectivity and high syncytium formation,also entered cells through clathrin-mediated endocytosis.These results provide new insights into SARS-CoV-2 cellular entry and present proof of principle that targeting viral entry could be an effective way to treat different variant infections.
文摘目的探讨替米沙坦干预对自发性高血压大鼠(SHR)血管组织血管紧张素转换酶2(ACE2)基因表达、一氧化氮(NO)及氧化应激水平的影响。方法选取10周龄SHR及其同源对照WKY大鼠,分别给予替米沙坦(5、10 mg.kg-1.d-1)或安慰剂,为期10周。采用Western blot检测治疗后大鼠主动脉组织中ACE2蛋白及内皮型NO合酶(eNOS)磷酸化水平。分别采用硝酸还原酶比色法与硫代巴比妥酸比色法测定大鼠主动脉组织中NO和丙二醛(MDA)含量。结果与WKY对照组相比,SHR大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平明显降低(ACE2:0.39±0.05vs 1.00±0.06;p-eNOS:0.43±0.06 vs 1.00±0.04;P值均<0.01),伴NO水平下调及MDA含量增加(NO mmol.g-1protein:11.5±2.1 vs 27.8±4.9;MDA nmol.g-1 protein:393.9±17.9 vs 186.3±14.5;P值均<0.01),而经替米沙坦治疗后SHR低、高剂量治疗组大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平增加(ACE2:0.62±0.06,0.65±0.07 vs 0.39±0.05;p-eNOS:0.68±0.07,0.71±0.06 vs0.43±0.06;P值均<0.05),伴NO水平升高(19.2±3.3,23.9±3.2 vs 11.5±2.1 mmol.g-1protein;P值均<0.05)与MDA含量下调(271.9±16.1,249.2±19.6 vs 393.9±17.9nmol.g-1protein;P值均<0.05)。结论长期替米沙坦治疗通过提升高血压大鼠血管ACE2表达及eNOS磷酸化水平,可促使血管NO生成及氧化应激水平改善,提示替米沙坦对高血压具有一定的血管保护功效。
