目的 研究单羰基姜黄素类似物(WZ35)对1型糖尿病小鼠糖尿病肾病(DN)的缓解作用。方法 采用ip链脲佐菌素(STZ)100 mg/kg方法制备1型糖尿病小鼠模型, 模型成功后分别ig给予姜黄素及WZ35(20 mg/kg), 连续给药9周。每周检测各组小鼠体质量和血糖, 实验结束时生化分析仪检测血清中肌酐(Cr)和尿素氮(BUN)水平, HE染色观察肾组织病理性损伤, 采用RT-qPCR检测肾脏组织中炎症因子和趋化因子基因表达;CD68免疫组化染色检测肾脏组织巨噬细胞浸润情况。结果 与对照组比较, 模型组小鼠体质量明显下降, 血糖明显升高, 肾脏指数明显增加, 血清中Cr和BUN水平明显升高, 肾脏病理性损伤明显, 肾脏组织中炎症因子和趋化因子基因表达明显增加, 肾脏组织巨噬细胞浸润增加。姜黄素及其类似物WZ35对模型小鼠体质量、血糖和肾脏指数无明显影响, 显著降低模型小鼠血清中Cr和BUN水平, 明显缓解糖尿病引起的肾组织损伤;显著抑制肾脏组织中炎症因子和趋化因子的基因表达及巨噬细胞浸润, 且WZ35作用更显著。结论 姜黄素类似物WZ35能够通过抑制炎症反应缓解1型糖尿病小鼠DN进程。

Objective To study the alleviation of curcumin analog WZ35 on type 1 diabetic nephropathy (DN). Methods Mice were treated with a single ip injection of streptozocin (STZ) to induce type 1 diabetes, while the control animals received the same volume of citrate buffer. The curcumin and its analog WZ35 (20 mg/kg) were ig administration for 9 weeks after the diabete obtained. The body weight and blood glucose were monitored every 7 d. Biochemistry analyzer was used to analyze the creatinine (Cr) and urea nitrogen (BUN) levels in serum. The histopathology of kidney tissue was detected by HE staining. RT-qPCR assay was used to evaluate the gene levels of inflammatory cytokines and chemokines. CD68 staining was used to evaluate the macrophages infiltration in kidney tissue. Results Compared with negative control, the mice in diabetic group showed the reduced body weight, increased blood glucose, high Cr and BUN levels in serum, renal pathological damage, and increased inflammatory gene, and macrophages infiltration in kidney. While the administration with curcumin and its analog WZ35 could obviously attenuate the DN through inhibiting Cr and BUN in serum while had no effect on the body weight and blood glucose. Compared with curcumin, WZ35 could inhibit the gene expression of inflammatory cytokines and chemokines as well as infiltration of macrophages. Conclusion The curcumin analog could attenuate DN through inhibiting inflammatory response.

"十二五"国家科技支撑计划(2011BAI04B04);浙江省自然科学基金项目(LY15H280014)