BACKGROUND Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes,and leads to apoptosis.Apoptosis is very important in regulating the homeostasis of the hepatobiliary system.Endoplasmic reticulum(...BACKGROUND Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes,and leads to apoptosis.Apoptosis is very important in regulating the homeostasis of the hepatobiliary system.Endoplasmic reticulum(ER)stress is one of the signaling pathways that induce apoptosis.Moreover,the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-induced apoptotic pathway is the main way;but its role in liver injury remains unclear.Yinchenhao decoction(YCHD)is a traditional Chinese medicine formula that alleviates liver injury and apoptosis,yet its mechanism is unknown.We undertook this study to investigate the effects of YCHD on the expression of ER stress proteins and hepatocyte apoptosis in rats with obstructive jaundice(OJ).AIM To investigate whether YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CCAAT/enhancer-binding protein homologous protein(CHOP)-growth arrest and DNA damage-inducible protein 34(GADD34)pathway and B cell lymphoma/leukemia-2 related X protein(Bax)/B cell lymphoma/leukemia-2(Bcl-2)ratio.METHODS For in vivo experiments,30 rats were divided into three groups:control group,OJ model group,and YCHD-treated group.Blood was collected to detect the indicators of liver function,and liver tissues were used for histological analysis.For in vitro experiments,30 rats were divided into three groups:G1,G2,and G3.The rats in group G1 had their bile duct exposed without ligation,the rats in group G2 underwent total bile duct ligation,and the rats in group G3 were given a gavage of YCHD.According to the serum pharmacology,serum was extracted and centrifuged from the rat blood to cultivate the BRL-3A cells.Terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling(TUNEL)assay was used to detect BRL-3A hepatocyte apoptosis.Alanine aminotransferase(ALT)and aspartate transaminase(AST)levels in the medium were detected.Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)analyses were used to detect protein and gene expression leve展开更多
目的：运用基因芯片技术研究针刺对应激性高血压前期大鼠心脏基因表达的影响。方法：9周龄雄性Wistar大鼠27只,随机分为空白组、模型组、针刺组,每组9只。造模方法：噪声结合足底电击刺激,造模周期为14天。造模同时,针刺组针刺曲池穴、...目的：运用基因芯片技术研究针刺对应激性高血压前期大鼠心脏基因表达的影响。方法：9周龄雄性Wistar大鼠27只,随机分为空白组、模型组、针刺组,每组9只。造模方法：噪声结合足底电击刺激,造模周期为14天。造模同时,针刺组针刺曲池穴、太冲穴进行干预,模型组和空白组每天只做与针刺组相同的抓取刺激。记录在造模前1天、第3、5、7、9、11、13、15天大鼠的血压变化,并观察行为改变。15天后取材,进行基因芯片分析。结果：造模开始后,空白组血压一直正常;第3天,模型组血压开始上升〉120 mm Hg,至第14天,血压持续升高并保持在前期高血压（120~139 mm Hg）状态（P〈0.01）,出现行为改变,提示造模成功。针刺干预第5天开始,针刺组血压低于模型组（P〈0.05）。第15天,模型组已达到高血压水平,针刺组血压虽然没有降至正常,但与模型组相比较差异有统计学意义（P〈0.05）。芯片结果显示：模型组和空白组比较,186个基因表达上调,135个基因表达下调;针刺组和模型组比较,138个基因表达上调,183个基因表达下调;钙卫蛋白（S100A8/A9）、硫氧还蛋白相互作用蛋白（TXNIP）随血压变化,与血压及靶器官损伤密切相关。结论：针刺太冲、曲池穴对于应激性高血压前期大鼠具有明显的降压效应,其机制可能与调控高血压相关基因TXNIP、S100A8/A9的表达有关。展开更多
AIM： To investigate electroacupunture（EA） at the acupoints of Stomach Meridian of Foot-Yangming（SMFY）, Gallbladder Meridian of Foot-Yangming（SMFY） on gastric mucosal intestinal trefoil factor （ITF） gene expre...AIM： To investigate electroacupunture（EA） at the acupoints of Stomach Meridian of Foot-Yangming（SMFY）, Gallbladder Meridian of Foot-Yangming（SMFY） on gastric mucosal intestinal trefoil factor （ITF） gene expression detection in stress-induced rats with gastric mucosal lesion, and to explore the regulatory mechanism and significance of EA-related gastric mucosal protective effect. METHODS： Forty rats were randomly divided into 4 groups： Blank group, Model group, Model group＋EA at acupoints of SMFY group（＂SMFY group＂）, and Model group＋EA at acupoints of GMFY group（GMFY group）. All rats （except blank group） were made model by water immersion and restraint stress （WRS）. Then the gastric mucosa tissue in each rat was taken off alter assessment of gastric mucosal lesion index（GUI）, and the expression of ITF mRNA of the tissues was detected by reverse transcdption-polymerase chain reaction（RT-PCR） method. RESULTS： Compared with Model group（S4.3± 1.34）, the GUI value in SMFY group （31±2.211 decreased significantly（P〈0.01）, so did that in GMFY group （39.8± 1.62, P〈0.05）, meanwhile GUI value in SMFY group was significantly lower than in GMFY group（P〈0.01）. Compared with Model group （0.65±0.01）, EA had a tendency to improve the expression of gastric mucosal ITFmRNA gene： such tendency existed in GMFY group （0.66±0.01） but with no signficant difference（P〉 0.05）, in SMFY group（0.76±0.01） with an extremely obvious difference （P〈0.01）, furthermore the expression in SMFY group was significantly higher than in GMFY group （P〈 0.01）.CONCLUSION： The gastric mucosal protective effect by EA at the acupoints of SMFY and GMFY was related to the expression variance of ITF, indicating certain meridian specificity exists, It could be one proof for the TCM theory ＂Relative pardcularity between SMFY and stomach＂.展开更多
为了探讨贵州万山汞矿汞污染生物健康效应,研究了万山8个月龄鸭子和万山粮食暴露20、30 d后大鼠脑、肝、血中MDA、SOD、GSH-px的变化以及大鼠大脑皮层中c-JUN蛋白表达.结果表明:在鸭血清、脑和肝组织中GSH-px和SOD活性与对照组相比均显...为了探讨贵州万山汞矿汞污染生物健康效应,研究了万山8个月龄鸭子和万山粮食暴露20、30 d后大鼠脑、肝、血中MDA、SOD、GSH-px的变化以及大鼠大脑皮层中c-JUN蛋白表达.结果表明:在鸭血清、脑和肝组织中GSH-px和SOD活性与对照组相比均显著升高(P<0.05),而MDA含量没有发生显著变化(P>0.05);万山组大鼠脑、肝、血中MDA、SOD、GSH-px的变化除暴露20 d MDA与对照组相比脑组织中含量显著升高(P<0.05)外,其他均无显著变化(P>0.05);大鼠大脑皮层c-JUN蛋白表达显著增加.从而可以推断,硒对汞引起的氧化损伤有很强的保护能力;汞对大鼠脑c-JUN蛋白表达的诱导不是或仅小部分由脂质过氧化所介导.展开更多
Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori infection.This bacterium promotes the production of reactive oxygen spec...Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori infection.This bacterium promotes the production of reactive oxygen species(ROS),which cause DNA damage in gastric epithelial cells.In this study,we evaluated the expression of important genes involved in the recognition of DNA damage(ATM,ATR,and H2AX)and ROS-induced damage repair(APE1)and the expression of some miRNAs(miR-15a,miR-21,miR-24,miR-421 and miR-605)that target genes involved in the DNA damage response(DDR)in 31 fresh tissues of gastric cancer.Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.Analysis performed by real-time quantitative PCR exhibited significantly increased levels of the APE1(RQ=2.55,p<0.0001)and H2AX(RQ=2.88,p=0.0002)genes beyond the miR-421 and miR-605 in the gastric cancer samples.In addition,significantly elevated levels of miR-21,miR-24 and miR-421 were observed in diffuse-type gastric cancer.Correlation analysis reinforced some of the gene:gene(ATM/ATR/H2AX)and miRNA:mRNA relationships obtained also with the interaction network.Thus,our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage,which could confer an advantage to cell survival and proliferation in the tumor microenvironment.展开更多
基金Supported by the National Natural Science Foundation of China,No.81273952
文摘BACKGROUND Chronic biliary obstruction results in ischemia and hypoxia of hepatocytes,and leads to apoptosis.Apoptosis is very important in regulating the homeostasis of the hepatobiliary system.Endoplasmic reticulum(ER)stress is one of the signaling pathways that induce apoptosis.Moreover,the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-induced apoptotic pathway is the main way;but its role in liver injury remains unclear.Yinchenhao decoction(YCHD)is a traditional Chinese medicine formula that alleviates liver injury and apoptosis,yet its mechanism is unknown.We undertook this study to investigate the effects of YCHD on the expression of ER stress proteins and hepatocyte apoptosis in rats with obstructive jaundice(OJ).AIM To investigate whether YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CCAAT/enhancer-binding protein homologous protein(CHOP)-growth arrest and DNA damage-inducible protein 34(GADD34)pathway and B cell lymphoma/leukemia-2 related X protein(Bax)/B cell lymphoma/leukemia-2(Bcl-2)ratio.METHODS For in vivo experiments,30 rats were divided into three groups:control group,OJ model group,and YCHD-treated group.Blood was collected to detect the indicators of liver function,and liver tissues were used for histological analysis.For in vitro experiments,30 rats were divided into three groups:G1,G2,and G3.The rats in group G1 had their bile duct exposed without ligation,the rats in group G2 underwent total bile duct ligation,and the rats in group G3 were given a gavage of YCHD.According to the serum pharmacology,serum was extracted and centrifuged from the rat blood to cultivate the BRL-3A cells.Terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling(TUNEL)assay was used to detect BRL-3A hepatocyte apoptosis.Alanine aminotransferase(ALT)and aspartate transaminase(AST)levels in the medium were detected.Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)analyses were used to detect protein and gene expression leve
文摘目的：运用基因芯片技术研究针刺对应激性高血压前期大鼠心脏基因表达的影响。方法：9周龄雄性Wistar大鼠27只,随机分为空白组、模型组、针刺组,每组9只。造模方法：噪声结合足底电击刺激,造模周期为14天。造模同时,针刺组针刺曲池穴、太冲穴进行干预,模型组和空白组每天只做与针刺组相同的抓取刺激。记录在造模前1天、第3、5、7、9、11、13、15天大鼠的血压变化,并观察行为改变。15天后取材,进行基因芯片分析。结果：造模开始后,空白组血压一直正常;第3天,模型组血压开始上升〉120 mm Hg,至第14天,血压持续升高并保持在前期高血压（120~139 mm Hg）状态（P〈0.01）,出现行为改变,提示造模成功。针刺干预第5天开始,针刺组血压低于模型组（P〈0.05）。第15天,模型组已达到高血压水平,针刺组血压虽然没有降至正常,但与模型组相比较差异有统计学意义（P〈0.05）。芯片结果显示：模型组和空白组比较,186个基因表达上调,135个基因表达下调;针刺组和模型组比较,138个基因表达上调,183个基因表达下调;钙卫蛋白（S100A8/A9）、硫氧还蛋白相互作用蛋白（TXNIP）随血压变化,与血压及靶器官损伤密切相关。结论：针刺太冲、曲池穴对于应激性高血压前期大鼠具有明显的降压效应,其机制可能与调控高血压相关基因TXNIP、S100A8/A9的表达有关。
基金Supported by the National Natural Science Foundation of China No. 90209023
文摘AIM： To investigate electroacupunture（EA） at the acupoints of Stomach Meridian of Foot-Yangming（SMFY）, Gallbladder Meridian of Foot-Yangming（SMFY） on gastric mucosal intestinal trefoil factor （ITF） gene expression detection in stress-induced rats with gastric mucosal lesion, and to explore the regulatory mechanism and significance of EA-related gastric mucosal protective effect. METHODS： Forty rats were randomly divided into 4 groups： Blank group, Model group, Model group＋EA at acupoints of SMFY group（＂SMFY group＂）, and Model group＋EA at acupoints of GMFY group（GMFY group）. All rats （except blank group） were made model by water immersion and restraint stress （WRS）. Then the gastric mucosa tissue in each rat was taken off alter assessment of gastric mucosal lesion index（GUI）, and the expression of ITF mRNA of the tissues was detected by reverse transcdption-polymerase chain reaction（RT-PCR） method. RESULTS： Compared with Model group（S4.3± 1.34）, the GUI value in SMFY group （31±2.211 decreased significantly（P〈0.01）, so did that in GMFY group （39.8± 1.62, P〈0.05）, meanwhile GUI value in SMFY group was significantly lower than in GMFY group（P〈0.01）. Compared with Model group （0.65±0.01）, EA had a tendency to improve the expression of gastric mucosal ITFmRNA gene： such tendency existed in GMFY group （0.66±0.01） but with no signficant difference（P〉 0.05）, in SMFY group（0.76±0.01） with an extremely obvious difference （P〈0.01）, furthermore the expression in SMFY group was significantly higher than in GMFY group （P〈 0.01）.CONCLUSION： The gastric mucosal protective effect by EA at the acupoints of SMFY and GMFY was related to the expression variance of ITF, indicating certain meridian specificity exists, It could be one proof for the TCM theory ＂Relative pardcularity between SMFY and stomach＂.
文摘为了探讨贵州万山汞矿汞污染生物健康效应,研究了万山8个月龄鸭子和万山粮食暴露20、30 d后大鼠脑、肝、血中MDA、SOD、GSH-px的变化以及大鼠大脑皮层中c-JUN蛋白表达.结果表明:在鸭血清、脑和肝组织中GSH-px和SOD活性与对照组相比均显著升高(P<0.05),而MDA含量没有发生显著变化(P>0.05);万山组大鼠脑、肝、血中MDA、SOD、GSH-px的变化除暴露20 d MDA与对照组相比脑组织中含量显著升高(P<0.05)外,其他均无显著变化(P>0.05);大鼠大脑皮层c-JUN蛋白表达显著增加.从而可以推断,硒对汞引起的氧化损伤有很强的保护能力;汞对大鼠脑c-JUN蛋白表达的诱导不是或仅小部分由脂质过氧化所介导.
基金financed by Sāo Paulo Research Foundation(FAPESP,grant number 2015/21464-0)Coordination for the Improvement of Higher Education Personnel(CAPES,grant number 1460154)the National Council for Scientific and Technological Development(CNPq,grant number 310120/2015-2).
文摘Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori infection.This bacterium promotes the production of reactive oxygen species(ROS),which cause DNA damage in gastric epithelial cells.In this study,we evaluated the expression of important genes involved in the recognition of DNA damage(ATM,ATR,and H2AX)and ROS-induced damage repair(APE1)and the expression of some miRNAs(miR-15a,miR-21,miR-24,miR-421 and miR-605)that target genes involved in the DNA damage response(DDR)in 31 fresh tissues of gastric cancer.Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.Analysis performed by real-time quantitative PCR exhibited significantly increased levels of the APE1(RQ=2.55,p<0.0001)and H2AX(RQ=2.88,p=0.0002)genes beyond the miR-421 and miR-605 in the gastric cancer samples.In addition,significantly elevated levels of miR-21,miR-24 and miR-421 were observed in diffuse-type gastric cancer.Correlation analysis reinforced some of the gene:gene(ATM/ATR/H2AX)and miRNA:mRNA relationships obtained also with the interaction network.Thus,our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage,which could confer an advantage to cell survival and proliferation in the tumor microenvironment.
