BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. ...BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. METHODS: Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacriifced 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were mea-sured with quantitative real-time RT-PCR and Western blotting. RESULTS: The serum aminotransferases level and scores of he-patic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P<0.01). Compared with the IR group, OA pretreatment signiifcantly up-regulated the expression of Sesn2, PI3K, Akt and HO-1 in IR livers (P<0.05). Administration of zinc protoporphyrin (ZnPP), an inhibitor of HO-1, diminished the OA effect on HO-1 and Sesn2 expressions (P<0.05) and the protective effect of OA on IRI. CONCLUSIONS: Our results demonstrate that OA can attenu-ate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.展开更多
The prevalence and lethality of chronic non-communicable diseases are constantly rising,becoming a global public health problem.The occurrence and development of chronic diseases are closely related to the generation ...The prevalence and lethality of chronic non-communicable diseases are constantly rising,becoming a global public health problem.The occurrence and development of chronic diseases are closely related to the generation of excessive free radicals and active oxygen in the body,and anti-oxidation will become an effective treatment.Sestrin2 protein,as a new stress protein found in mammals in recent years,has unique advantages in antioxidants,and is expected to become an effective biomarker and therapeutic target for chronic diseases.The following is a review of the regulatory role and mechanism of sestrin2 in chronic diseases in order to provide a reference for the research of other scholars.展开更多
基金supported by grants from the Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials,Basic Research Program-Youth Fund Project of Jiangsu Province(BK20140092)the National Natural Science Foundation of China(81400650,81470901,81273261 and 81270583)
文摘BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. METHODS: Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacriifced 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were mea-sured with quantitative real-time RT-PCR and Western blotting. RESULTS: The serum aminotransferases level and scores of he-patic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P<0.01). Compared with the IR group, OA pretreatment signiifcantly up-regulated the expression of Sesn2, PI3K, Akt and HO-1 in IR livers (P<0.05). Administration of zinc protoporphyrin (ZnPP), an inhibitor of HO-1, diminished the OA effect on HO-1 and Sesn2 expressions (P<0.05) and the protective effect of OA on IRI. CONCLUSIONS: Our results demonstrate that OA can attenu-ate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.
文摘探讨Sestrin2蛋白(Sesn2蛋白)在2型糖尿病(Type 2 diabetes mellitus,T2DM)合并冠心病(Coronary heart disease,CHD)患者血清中的变化趋势。方法 选取2021.06至2022.06于我院就诊的142例患者,依据患者有无T2DM、CHD将其分为T2DM组(DM组,n=50),CHD组(CHD组,n=45),T2DM合并CHD组(DC组,n=47),另选取同期同年龄阶段于我院就诊的健康人群为对象组(NC组,n=48)。收集并分析所有受试者的一般资料及生化指标,ELISA法检测Sesn2蛋白水平,利用Sperman相关分析、多元逐步回归分析探讨血清Sesn2蛋白与生化指标的关系。结果 DC组Sesn2蛋白水平较余三组明显降低[4.41±0.88 vs 3.08±0.90 vs 2.78±0.63 vs 2.41±0.42(P<0.05)],Sperman相关分析示SBP、FPG、HbA1c、FINS、HOMA-IR、LDL、TG与血清Sesn2蛋白水平呈负相关(P<0.05),多元线性回归分析示影响血清Sesn2表达的因素为HbA1c、LDL(P<0.05)。结论 Sesn2蛋白可通过AMPK途径抑制mTORC1产生,进而影响T2DM及CHD的发生发展。
基金Subproject of National High-tech R&D Program of China(863 Program)(No.2011 AA02A111)。
文摘The prevalence and lethality of chronic non-communicable diseases are constantly rising,becoming a global public health problem.The occurrence and development of chronic diseases are closely related to the generation of excessive free radicals and active oxygen in the body,and anti-oxidation will become an effective treatment.Sestrin2 protein,as a new stress protein found in mammals in recent years,has unique advantages in antioxidants,and is expected to become an effective biomarker and therapeutic target for chronic diseases.The following is a review of the regulatory role and mechanism of sestrin2 in chronic diseases in order to provide a reference for the research of other scholars.