Regulating mechanism of Qishen Yiqi Dripping Pills on mitochondrial autophagy in type 2 diabetic rats / 国际生物医学工程杂志

ABSTRACT

Objective:To observe the protective effect of Qishen Yiqi Dripping Pills on myocardial ischemia-reperfusion injury in type 2 diabetic rats and its effects on mitochondrial autophagy phosphoglycerate mutase family member 5 (PGAM5)/Fun14 domain-containing protein 1 (FUNDC1) signaling pathway.Methods:48 male SD rats were divided into a blank control group, sham operation group, No.1 myocardial ischemia reperfusion injury (MIRI) group, No.2 MIRI group, inhibitor group, and Qishen Yiqi group. In addition to the blank control group and the No.1 MIRI group, the other 32 rats were fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish animal models of diabetes. Then, the rats in the Qishen Yiqi group were ig Qishen Yiqi Gropping Pills 450 mg/kg, once daily. The rats in the inhibitor group were given Qishen Yiqi Gropping Pills and trimethylamine (3-MA) by intraperitoneal injection 100 mmol/L, once daily. And the rats in the other four groups were ig normal saline. One week after intragastric administration, except for the blank control group and the sham operation group, the rats in the other four groups were used to establish the animal model of myocardial ischemia-reperfusion injury by ligating the anterior descending branch of the left coronary artery for 30 min and reperfusion for 2 h. Then, the materials were taken after reperfusion for 2 h. Finally, the mortality of rats was calculated, the changes in creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected, and the expression level of PGAM5/FUNDC1 pathway node protein in myocardial tissue was measured by real-time fluorescence quantitative PCR.Results:Compared with the No.1 MIRI group, serum indicators of the AST, LDH, CK, and MDA levels in the No.2 MIRI model group increased (all P < 0.05), while the level of SOD decreased ( P < 0.05). Compared with the No.1 MIRI group, myocardial tissue indicators of FUNDC1, PGAM5, B cell lymphoma-xL (Bcl-xL), light chain 3 (LC3), autophagy associated protein 5 (ATG5), and Beclin-1 level decreased (all P < 0.05), the level of P62 increased ( P < 0.05), while the level of cysteinyl aspartate specific proteinase-9 (Caspase-9) increased, but he difference is not statistically significant ( P > 0.05). Compared with the No.2 MIRI group and the inhibitor group, serum indicators of the AST, LDH, CK, and MDA levels in the Qishen Yiqi group decreased (all P < 0.05), and the level of SOD increased ( P < 0.05). Compared with the No.2 MIRI group and the inhibitor group, myocardial tissue indicators of FUNDC1, PGAM5, Bcl-xL, LC3, ATG5, and Beclin-1 levels increased (all P < 0.05), while the levels of P62 and Caspase-9 decreased (all P < 0.05). Conclusions:High blood sugar levels can aggravate MIRI. Qishen Yiqi Dripping Pills can regulate mitochondrial autophagy through the PGAM5/FUNDC1 pathway and alleviate myocardial ischemia-reperfusion injury. MIRI plays a protective role in the myocardium of diabetic rats.