Lu Yan-Zhen, Wang Jia, Song Juan, Li Bao-Hong, Guo Ya-Ling, Wang Dong, Zhang Cui-Ying
Department of Pathophysiology, Changzhi Medical College, Changzhi 046000, China.
Department of Immunology, Changzhi Medical College, Changzhi 046000, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2016 Apr 8;32(4):351-355. doi: 10.13459/j.cnki.cjap.2016.04.017.
To study the role of Notch1 signaling pathway in the myocardial protective effects of resveratrol pro-treatment after hepatic ischemia/reperfusion injury.
Thirty-six healthy male SD rats were randomly divided into 3 groups:sham control (SC) group, hepatic ischemic/reperfusion (HIR) group, and pro-treatment resveratrol (Res) group,12 rats in each group. After each group with hepatic ischemia 40 min reperfusion 2 h (SC group placing equal time), the left ventricular function including left ventricular pressure (LVP), left ventricular systolic pressure (LVSP) and its derivate (±dp/dt) was measured; the serum activities of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) and tumor necrosis factorα(TNF-α) and interleukin-6(IL-6) were detected. The activity of myocardial su-peroxide dismutase(SOD) and contents of myocardial malonaldehyde (MDA) were determined; Notch intracellular domain (NICD) expressions were detected with Western blot; the mRNA levels of Notch1 and TNF-αwere detected by real-time PCR.
Compared with SC group, the left ventricular functions in the HIR group were significantly decreased. With decreasing the expression of NICD and Notchl, the activities of CK-MB, LDH, TNF-αand IL-6 in the serum were evidently increased(<0.01), the activity of SOD in myocardum was decreased and contents of MDA in myocardum was enhanced (<0.01). Compared with HIR group, the left ventricular functions were significantly en-hanced in Res group (<0.01). The above mentioned parameters in the serum in the Res group were evidently improved (<0.01), meanwhile the expression of NICD and Notchl were significantly enhanced whereas the expression of TNF-α was obviously decreased.
The findings indicate that resveratrol has protective effect on myocardial injury during the hepatic ischemia/reperfusion, and its mecha-nisms may be related to anti-inflammation and anti-oxidative stress Notch signaling pathway.
研究Notch1信号通路在肝缺血/再灌注损伤后白藜芦醇预处理心肌保护作用中的作用。
将36只健康雄性SD大鼠随机分为3组:假手术对照组(SC组)、肝缺血/再灌注(HIR)组和白藜芦醇预处理(Res)组,每组12只。各组肝缺血40分钟再灌注2小时后(SC组放置相同时间),测量左心室功能,包括左心室压力(LVP)、左心室收缩压(LVSP)及其导数(±dp/dt);检测血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)的活性。测定心肌超氧化物歧化酶(SOD)活性和心肌丙二醛(MDA)含量;用蛋白质印迹法检测Notch细胞内结构域(NICD)表达;用实时PCR检测Notch1和TNF-α的mRNA水平。
与SC组相比,HIR组左心室功能明显降低。随着NICD和Notch1表达降低,血清中CK-MB、LDH、TNF-α和IL-6活性明显升高(P<0.01),心肌SOD活性降低,心肌MDA含量升高(P<0.01)。与HIR组相比,Res组左心室功能明显增强(P<0.01)。Res组血清中上述参数明显改善(P<0.01),同时NICD和Notch1表达明显增强,而TNF-α表达明显降低。
研究结果表明,白藜芦醇对肝缺血/再灌注期间的心肌损伤具有保护作用,其机制可能与抗炎和抗氧化应激Notch信号通路有关。