Protective effects of HMS5552 on pancreatic β cell injury in diabetic rats
Objective To investigate the protective effect of HMS5552 on pancreatic islet β-cell injury in diabetic rats and study the mechanism.Methods A total of 40 SD rats were fed with high-sugar and high-fat diet for 8 weeks combined with intraperitoneal injection of streptozotocin(STZ)to induce type 2 diabetic rat models.The successful model rats were divided into model group(0.9％NaCl by gavage)and experimental group(30 mg·kg-1 HMS5552 by gavage).The other 20 normal rats served as the normal group(0.9％NaCl was given by gavage).Hematoxylin-eosin(HE)staining was used to detect the pathological changes of pancreatic islets.The INS-1 cells were divided into blank group(normal cultured),model group(high-sugar and high-fat culture medium)and experimental-L,-M,-H groups(high-sugar and high-fat culture medium+0.3,3.0 and 30.0 μmol·L-1 HMS5552).The viability of INS-1 cells was detected by cell counting kit-8(CCK-8)method,the apoptosis of INS-1 cells was detected by Annexin V/PI method,the mRNA expression level of B cell lymphocytoma 2(Bcl-2)was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)method;the expression level of phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway and apoptosis protein was detected by western blotting.Results HE staining showed that the pathological damage of pancreas in the experimental group rats was significantly less than that in the model group.The cell viability of the blank group,model group and experimental-L,-M,-H groups were(99.67±2.40)％,(48.18±4.18)％,(61.74±4.78)％,(70.74±6.36)％and(78.30±4.68)％,respectively;apoptosis rates were(10.40±4.66)％,(48.60±3.27)％,(35.90±4.45)％,(28.07±5.35)％and(18.30±3.04)％,respectively;the relative expression levels of Bcl-2 mRNA were 1.00±0.03,0.32±0.04,0.59±0.05,0.62±0.04 and 0.72±0.12,respectively;phosphorylated PI3K(p-PI3K)/PI3K ratios were 1.00±0.00,0.34±0.05,0.46±0.02,0.64±0.01 and 0.81±0.01,respectively;phosphorylated AKT(p-AKT)/AKT ratios were 1.00±0.00,0.28±0.12,0.63±0.02,0.74±0.06 and 0.87±0.09,respectively.The above indexes in the model group compared with the blank group,the differences between the above indexes of the experimental-L,-M,-H groups and the model group were statistically significant(P＜0.05,P＜0.01).Conclusion HMS5552 can improve glucose metabolism in diabetic rats and protect pancreatic β-cells by regulating the expression of PI3K/AKT signaling pathway.
万方数据
维普
