关键词: 横纹肌溶解, 急性肾损伤, 溶酶体相关膜蛋白质2, 组织蛋白酶B, 山莨菪碱, 肌红蛋白, 氧化应激

Abstract: Objective　To observe the effect of anisodamine on the expressions of lysosome associated membrane protein-2 and cathepsin B in acute renal tubular epithelial cells induced by inrhabdomyolysis in rats and explore the mechanism. Methods　Sixty-three male Sprague-Dawley rats were randomly divided into control group, model group and administration group. The rat model of acute kidney injury induced by rhabdomyolysis was established by glycerol intramuscular injection in the model group and the administration group, while the administration group was given anisodamine by intraperitoneal injection (1 mg/kg) before the initial glycerol injection. At different time points after glycerol injection, HE staining was used to observe the pathological changes of kidney tissues. The renal function indicators including serum urea nitrogen (BUN), serum creatinine (Scr), creatine kinase (CK) and serum myoglobin (Mb) were measured. The contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in kidney tissues were detected. After acute kidney injury was induced by intramuscular injection of glycerol for 24 h, the expressions of LAMP2, Cathepsin B and Megalin in kidney tissues were detected by immunohistochemistry and Western blot assay. Results　HE staining indicated that the rats in the model group had obvious kidney injury. However, anisodamine significantly ameliorated kidney injury. The serum BUN levels of 12 h and 24 h, Scr of 24 h and 48 h, CK of 6 h, and Mb of 24 h were significantly higher in model group than those of the control group (P＜0.05). In contrast, all of these markers at the corresponding time points were significantly ower in anisodamine administration group than those of the model group (P＜0.05). In comparison to the model group, the MDA content was significantly decreased at 6 h and 12 h in the administration group (P＜0.05), while SOD activity was significantly increased (P＜0.05). In addition, the results of immunohistochemistry and Western blot assay showed that the expression levels of LAMP2, Cathepsin B and Megalin at 24 h were significantly higher in the model group than those of the control group and the administration group. However, the expression levels of these proteins in the administration group were significantly lower than those in the model group (P＜0.05). Conclusion　Anisodamine could perform a protective role to kidney by reducing the production of Mb, down-regulating the expressions of LAMP2 and Cathepsin B in renal tissues and restraining oxidative stress.

Key words: rhabdomyolysis, acute kidney injury, lysosomal-associated membrane protein 2, Cathepsin B, anisodamine, myoglobin, oxidative stress