Study on the Mechanism of Shenqi Tangluo Pill Improving Hepatocyte Apoptosis in Obese Diabetes Mice by Regulating PI3K/Akt Pathway

OBJECTIVE To investigate the effect and mechanism of Shenqi Tangluo pill on improving apoptosis of liver cells in obese diabetes mellitus by regulating PI3K/Akt pathway.

METHODS The 60 SPF grade 7-week-old db/db mice were included in the experiment and randomly divided into model control group, positive control group and Shenqi Tangluo pill high-dose, medium-dose and low-dose groups. The 12 db/m mice of the same age were selected as blank control group. Positive control group was given metformin(0.26 g·kg⁻¹) by gavage, Shenqi Tangluo pill high, medium and low dose groups were given different concentrations of Shenqi Tangluo pill(76, 38, 19 g·kg⁻¹) by gavage, blank control group and model control group were given the same amount of distilled water by gavage every day, and the intervention lasted for 8 weeks. The living state of the mice was observed and body weight and fasting blood glucose(FBG) were measured. The contents of AST and ALT in liver were detected by biochemical kit. Hematoxylin-eosin(HE), oil red O and TUNEL staining were used to observe the pathological changes, fat accumulation and apoptosis of liver tissues in each group. The expression levels of Bax and Bcl-2 protein in liver tissues were analyzed by immunohistochemical staining(IHC). The expression level of PI3K, p-Akt, Caspase-3 protein in liver tissues of mice in each group was detected by Western blotting.

RESULTS  Compared with the blank control group, the body weight of mice in the model control group significantly increased(P<0.05); FBG significantly increased(P<0.05); AST and ALT in liver tissue significantly increased(P<0.05); liver pathology and oil red O staining showed a significant increase in the degree of hepatic steatosis and disordered hepatocyte structure; the apoptosis rate of liver cells significantly increased(P<0.05); the expression levels of Caspase-3 and Bax proteins in liver tissue significantly increased(P<0.05); the expression levels of PI3K, p-Akt, and Bcl-2 proteins significantly decreased(P<0.05); and the Bax/Bcl-2 ratio significantly increased(P<0.05). Compared with the model control group, the body weight of mice in the high- and medium-dose groups of Shenqi Tangluo pill significantly decreased(P<0.05); FBG significantly decreased(P<0.05); the apoptosis rate of liver cells significantly decreased(P<0.05); the degree of liver structural damage in each treatment group was significantly reduced, and the extent of fatty degeneration was alleviated; AST and ALT levels in liver tissue significantly decreased(P<0.05); the expression levels of Bax and Caspase-3 in liver tissue significantly decreased(P<0.05); the expression levels of PI3K, p-Akt, and Bcl-2 significantly increased(P<0.05); and the Bax/Bcl-2 ratio significantly decreased(P<0.05).

CONCLUSION Shenqi Tangluo pill can improve blood sugar and liver steatosis in mice with obesity diabetes mellitus, and its mechanism may be related to regulating PI3K/Akt pathway and inhibiting hepatocyte apoptosis.