Inhibitory effect of valsartan on endoplasmic reticulum stress and inflammation in the diabetic rat kidney / 中国实验动物学报

ABSTRACT

Objective To study the role of endoplasmic reticulum stress and related inflammation in the kidneys of rats with diabetic nephropathy and the effect of valsartan on these lesions.Methods The diabetic rat model was induced by intraperitoneal injection of streptozotocin.Thirty-four healthy male SD rats were randomly divided into normal control group (n=10), diabetic group (n=12), and valsartan group (n=12).Valsartan (10 mg/kg) was administered daily by gavage from the next day of the diabetes induction for 6 weeks.The expression and distribution of ERS-related proteins P-IRE1α, P-JNK, and MCP-1 were examined by immunohistochemistry and Western blot.Real-time fluorescence quantita-tive PCR was used to detect the mRNA expressions of IRE1α, JNK and MCP-1.The 24-hour urine protein excretion, Scr, and BUN were checked.Results Compared with the control group, infiltration of inflammatory cells was aggravated in the kidneys of DM+V group, the expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly increased, and the levels of IRE1mRNA and MCP-1mRNA increased compared with the DM group, infiltration of inflammation cells was alleviated in the kidney of DM+V group, the protein expressions of P-IRE1α,IRE1α,P-JNK,MCP-1 were significantly reduced, the levels of IRE1mRNA and MCP-1mRNA were reduced.While there was no significant difference in the expression of JNK mRNA and protions among the three groups.Conclusions ERS and related inflammation are activated in the kidney of di-abetic rats.Inhibition of the IRE1/JNK/MCP-1 pathway of ERS and related inflammation might be responsible for the pro-tective effects of valsartan on the kidneys of diabetic rats.