[关键词]
[摘要]
目的 探讨川芎嗪通过抑制NF-κB信号途径减轻膜性肾病大鼠的炎性反应和肾损伤的作用和机制。方法 Wistar大鼠分为对照组、模型组和川芎嗪低、高剂量(60、120 mg/kg)组,称量各组大鼠的体质量和肾脏质量,计算肾脏系数;双缩脲法测定各组大鼠24 h尿蛋白水平;全自动生化分析仪检测各组大鼠血清肌酐、尿素氮(BUN)、脂联素、总胆固醇(TC)、三酰甘油(TG)水平;HE染色观察各组大鼠肾组织病理变化;实时荧光定量PCR(qRT-PCR)法检测各组大鼠肾组织中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和巨噬细胞趋化蛋白-1(MCP-1)mRNA的表达;ELISA法检测各组大鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)的表达;免疫组织化学法检测各组大鼠肾组织中p-NF-κB的表达;Western blotting检测各组大鼠肾组织中p-NF-κB蛋白的表达。结果 与模型组比较,川芎嗪低、高剂量组大鼠的肾质量及肾脏系数均显著降低(P<0.05、0.01),尿蛋白和血清肌酐、BUN、脂联素、TC、TG水平显著下调(P<0.05、0.01),肾组织病理损伤明显减轻,肾小球基底膜增厚和肾小球萎缩减轻,肾组织中TNF-α、IL-1β、MCP-1 mRNA的表达水平显著下降(P<0.05、0.01),血清中MDA水平显著下调,SOD水平显著上调(P<0.05、0.01),肾组织p-NF-κB的表达水平显著下调(P<0.05、0.01)。结论 川芎嗪对大鼠膜性肾病有较好的治疗效果,调节炎性因子的表达、改善肾脏组织形态,其机制与NF-κB通路有关。
[Key word]
[Abstract]
Objective To investigate the effects and mechanisms of ligustrazine on reducing inflammatory response and renal injury in rats with membranous nephropathy by inhibiting the NF-κB signaling pathway. Methods Wistar rats were divided into control group, model group, ligustrazine low and high dose (60 and 120 mg/kg) group. Weigh the body weight and kidney weight of each group of rats and calculate the renal body cell index; Biuret method was used to determine the 24 h urine protein level of rats in each group; Automatic biochemical analyzer was used to detect serum creatinine, serum urea nitrogen (BUN), adiponectin, total cholesterol, and serum triglyceride in each group of rats; HE staining was used to observe the pathological changes of kidney tissue in each group of rats; qRT-PCR was used to detect the expression of TNF-α, IL-1β and MCP-1 in kidney tissues of rats in each group; ELISA was used to detect the expression of MDA and SOD in the serum of each group of rats; Immunohistochemical method was used to detect the expression of p-NF-κB in kidney tissue of rats in each group; Western blot was used to detect the expression of p-NF-κB protein in rat kidney tissues. Results Compared with model group, the renal mass and renal coefficient of rats in ligustrazine low-dose and high-dose groups were significantly decreased (P < 0.05, 0.01), the levels of urinary protein and serum creatinine, BUN, adiponectin, TC and TG were significantly decreased (P < 0.05, 0.01), and the pathological damage of renal tissue was significantly alleviated. The expression levels of TNF-α, IL-1β and MCP-1 mRNA in renal tissue were significantly decreased (P < 0.05, 0.01), and the level of MDA in serum was significantly decreased. SOD level was significantly up-regulated (P < 0.05, 0.01), and the expression level of P-NF-κB in renal tissue was significantly down-regulated (P < 0.05, 0.01). Conclusion Ligustrazine has a good therapeutic effect on membranous nephritis in rats, regulates the expression of inflammatory factors, and improves the kidney tissue morphology in rats, which may be related to the NF-κB pathway.
[中图分类号]
R285.5
[基金项目]
陕西省重点研发计划项目(2019SF-144)