目的 探討川芎嗪通過抑制NF-κB信號途徑減輕膜性腎病大鼠的炎性反應(yīng)和腎損傷的作用和機制。方法 Wistar大鼠分為對照組、模型組和川芎嗪低、高劑量（60、120 mg/kg）組，稱量各組大鼠的體質(zhì)量和腎臟質(zhì)量，計算腎臟系數(shù)；雙縮脲法測定各組大鼠24 h尿蛋白水平；全自動生化分析儀檢測各組大鼠血清肌酐、尿素氮（BUN）、脂聯(lián)素、總膽固醇（TC）、三酰甘油（TG）水平；HE染色觀察各組大鼠腎組織病理變化；實時熒光定量PCR（qRT-PCR）法檢測各組大鼠腎組織中腫瘤壞死因子（TNF）-α、白細胞介素（IL）-1β和巨噬細胞趨化蛋白-1（MCP-1）mRNA的表達；ELISA法檢測各組大鼠血清中丙二醛（MDA）、超氧化物歧化酶（SOD）的表達；免疫組織化學法檢測各組大鼠腎組織中p-NF-κB的表達；Western blotting檢測各組大鼠腎組織中p-NF-κB蛋白的表達。結(jié)果 與模型組比較，川芎嗪低、高劑量組大鼠的腎質(zhì)量及腎臟系數(shù)均顯著降低（P<0.05、0.01），尿蛋白和血清肌酐、BUN、脂聯(lián)素、TC、TG水平顯著下調(diào)（P<0.05、0.01），腎組織病理損傷明顯減輕，腎小球基底膜增厚和腎小球萎縮減輕，腎組織中TNF-α、IL-1β、MCP-1 mRNA的表達水平顯著下降（P<0.05、0.01），血清中MDA水平顯著下調(diào)，SOD水平顯著上調(diào)（P<0.05、0.01），腎組織p-NF-κB的表達水平顯著下調(diào)（P<0.05、0.01）。結(jié)論 川芎嗪對大鼠膜性腎病有較好的治療效果，調(diào)節(jié)炎性因子的表達、改善腎臟組織形態(tài)，其機制與NF-κB通路有關(guān)。

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.

R285.5

陜西省重點研發(fā)計劃項目（2019SF-144）