Ⅱ型糖尿病对小鼠肝脏Cx43蛋白表达及肝纤维化的影响  

Effects of typeⅡdiabetes on hepatic Cx43 protein expression and liver fibrosis in mice

作　　者：陆宣兆 柴晓明 任朝兴 朱志铭 李佳琪 黄鹭铭 莫廷美 马博[1] LU Xuanzhao;CHAI Xiaoming;REN Chaoxing;ZHU Zhiming;LI Jiaqi;HUANG Luming;MO Tingmei;MA Bo(School of Pharmaceutical Sciences,Nanjing Tech University,Nanjing 211800,China)

机构地区：[1]南京工业大学药学院,江苏南京211800

出　　处：《生物加工过程》2022年第6期665-671,共7页Chinese Journal of Bioprocess Engineering

基　　金：2020年江苏省研究生科研计划(KYCX20_1121)。

摘　　要：采用高脂饲料喂养结合链脲佐菌素(STZ)诱导法,建立Ⅱ型糖尿病小鼠动物模型。模型成功建立8周后,检测小鼠血清中葡萄糖、糖化血清蛋白(GSP)、谷草转氨酶(AST)、谷丙转氨酶(ALT)、碱性磷酸酶(AKP)的含量;以苏木精-伊红染色和油红O染色分别观察肝脏组织病理学变化和脂质沉积情况;以Masson染色结合α平滑肌动蛋白(α-SMA)及E-钙黏蛋白(E-cadherin)的免疫组织化学观察肝脏纤维化程度;以蛋白免疫印迹、免疫组化和实时荧光定量PCR分别检测肝脏缝隙连接蛋白43(Cx43)和基因表达。结果表明:与正常组相比,模型组小鼠的血糖、糖化血清蛋白显著升高;肝脏肿大色泽不均,血清AST、ALT、AKP水平显著升高;肝脏组织形态上有所改变,脂质沉积增加;胶原纤维分布显著增加,并且Ⅱ型糖尿病导致了α-SMA表达的增加,E-cadherin表达显著降低;肝组织Cx43表达显著增加。研究结果表明:长期的高血糖易导致小鼠肝损伤和纤维化,从而诱发糖尿病肝病,其肝脏纤维化的机制可能与高血糖诱导Cx43的表达密切有关。We detected the expression of Cx43 during the formation of liver fibrosis in typeⅡdiabetic mice,and explored the role of Cx43 in the occurrence and development of diabetic liver fibrosis.The animal model of typeⅡdiabetes was established by high-fat diet combined with Streptozocin(STZ)induction method.After the model was successfully established for 8 weeks,the contents of glucose,glycosylated serum protein(GSP),aspartate aminotransferase(AST),alanine aminotransferase(ALT),and alkaline phosphatase(AKP)in the mouse serum were detected;hematoxylin-eosin staining and oil red O staining were used to investigate the pathological changes of liver tissues and lipid deposition;we used masson staining combined withα-SMA and E-cadherin immunohistochemistry to observe the degree of liver fibrosis;western blot and real-time fluorescent quantitative PCR were used to detect the expression of liver Cx43.Compared with the normal control group,the blood glucose and glycosylated serum protein of the model group increased significantly;the liver index increased significantly,the liver was enlarged and the color was uneven,and the serum aspartate aminotransferase,alanine aminotransferase,and alkaline phosphatase levels were significantly increased.Liver tissue lipid deposition increased,collagen fiber distribution significantly increased;and typeⅡdiabetes caused an increase in the expression ofα-SMA,and a significant decrease in the expression of E-cadherin.Long-term hyperglycemia can easily lead to liver damage and fibrosis,and induce diabetic liver disease.The mechanism of liver fibrosis may be closely related to the expression of Cx43 induced by hyperglycemia.

关 键 词：Ⅱ型糖尿病 肝损伤 肝纤维化 缝隙连接蛋白43 

分 类 号：R965[医药卫生—药理学]