厄贝沙坦对糖尿病大鼠心肌损伤中MAPKs信号通路及相关因子的影响

李辉; 康品方; 徐庆梅; 戎李; 孙硕; 张冰; 高琴; 高大胜; 王洪巨

doi:10.13898/j.cnki.issn.1000-2200.2020.11.001

厄贝沙坦对糖尿病大鼠心肌损伤中MAPKs信号通路及相关因子的影响

Effect of irbesartan on the MAPKs signaling pathway and related factors in myocardial injury of diabetic rats

摘要

摘要:
目的观察厄贝沙坦在糖尿病大鼠心肌损伤中发挥的作用，并探讨其对丝裂原活化蛋白激酶(mitogen-activated protein kinase，MAPKs)信号通路及其相关因子表达影响。
方法雄性SD大鼠50只，随机分为糖尿病4周(DM4W)组、糖尿病8周(DM8W)组、糖尿病8周+厄贝沙坦(DM8W+Ir)组、对照(Con)组、高糖高胆固醇饮食(HC)组，各10只。复制2型糖尿病大鼠模型成功后，DM8W+Ir组给予厄贝沙坦溶液灌胃干预；饲喂第4周时，处死DM4W组大鼠并留取心脏组织标本；饲喂8周后，处死剩余组大鼠。比较各组大鼠空腹血糖、体质量、心体比和左心室质量指数；取大鼠离体心肌行Masson染色观察心肌细胞纤维化改变；ELISA法检测心肌细胞内炎症细胞因子白细胞介素(interleukin，IL)-1β、IL-6、IL-1表达水平；Western blotting法检测心肌组织丝裂原活化蛋白激酶磷酸酶-1(mitogen-activated protein kinase phosphatase-1，MKP-1)、P38丝裂原激活蛋白激酶(P38 mitogen-activated protein kinase，P38MAPK)、细胞外信号调节激酶(extracellular signal-related kinases，P-ERK1/2)蛋白表达水平。
结果HC组大鼠空腹血糖、体质量、心体比、左心室质量指数与Con组差异均无统计学意义(P>0.05)，IL-1β、IL-6、IL-1表达水平和MKP-1、P38MAPK、P-ERK1/2蛋白表达与Con组差异亦均无统计学意义(P>0.05)。与Con组、HC组相比，各糖尿病组大鼠Masson染色心肌细胞明显纤维化改变；体质量减轻，心肌细胞内炎症细胞因子IL-1β、IL-6、IL-1表达水平升高，心肌组织MKP-1蛋白表达降低，P38MAPK、P-ERK1/2蛋白表达升高(P < 0.05~P < 0.01)；与DM4W、DM8W组比较，DM8W+Ir组大鼠IL-1β、IL-6、IL-1表达水平降低，MKP-1蛋白表达升高，P38MAPK、P-ERK1/2表达蛋白降低(P < 0.05~P < 0.01)。
结论厄贝沙坦通过调控MAPKs信号通路发挥改善糖尿病心肌损伤的作用。

Abstract:
ObjectiveTo observe the effects of irbesartan on myocardial injury in diabetic rats, and to explore the effect of irbsartan on MAPKs signaling pathway and related factors expression.
MethodsFifty male SD rats were randomly divided into the four weeks of diabetes (DM4W) group, eight weeks of diabetes(DM8W) group, eight weeks of diabetes + irbesartan(DM8W+Ir) group, control(Con) group and high sugar and cholesterol diet(HC) group(10 rats in each group).After the model of type 2 diabetic rats were successfully established, the DM8W+Ir group was administered using irbesartan solution by gavage.At the fourth week of feeding, the DM4W group was sacrificed, and heart tissue specimens were collected.After 8 weeks of feeding, the remaining rats were sacrificed.The fasting blood glucose(FBG), body weight(BW), heart to body ratio(H/B) and left ventricular mass index(LVWI) were compared among five groups.The Masson staining was used to observe the changes of myocardial fibrosis in isolated rat myocardium.The levels of IL-1β, IL-6, IL-1 and IL-1 were detected using ELISA.Western blotting was used to detect the expression levels of mitogen-activated protein kinase-1(MKP-1), P38 mitogen-activated protein kinase(P38MAPK) and extracellular signal-related kinases(P-ERK1/2) in myocardium.
ResultsThere was no statistical significance in the levels FBG, BW, H/B, LVWI, IL-1β, IL-6 and IL-1, MKP-1, and protein levels of P38MAPK, P-ERK1/2 between HC group and Con group(P>0.05).Compared with the Con group and HC group, the fibrotic changes of Masson staining myocardial cells were observed, the body weight lightened, the expression levels of inflammatory cytokines IL-1, IL-6 and IL-1 in myocardial cells increased, the protein expression levels of MKP-1 in myocardial tissues decreased, and the protein expression levels of P38MAPK and P-ERK1/2 increased in diabetic rats(P < 0.05 to P < 0.01).Compared with the DM4W and DM8W groups, the expression levels of IL-1 β, IL-6 and IL-1 decreased, the expression level of MKP-1 protein increased, and the expression levels of P38MAPK and P-ERK1/2 decreased in DM8W+Ir group(P < 0.05 to P < 0.01).
ConclusionsIrbesartan can improve the diabetic myocardial injury by regulating the MAPKs signaling pathway.

HTML全文

参考文献(15)

施引文献

资源附件(0)