健脾清化方在肾小球硬化大鼠中抗肾纤维化的作用及其机制

Effects and Mechanism of “Jianpi Qinghua Decoction” on Renal Fibrosis in Rats with Glomerulosclerosis

目的观察健脾清化方对肾切除联合阿霉素诱导局灶节段性肾小球硬化模型大鼠总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)及肾组织肿瘤坏死因子-α(TNF-α)表达的影响,探讨该方抗肾纤维化的机制。方法将56只雄性SD大鼠分为正常组、假手术组、模型组、健脾清化方组、益气健脾组、清热化湿组和尿毒清组,每组8只。后5组行单侧肾切除合并阿霉素(3 mg/kg)尾静脉注射建立大鼠肾硬化模型,分别给予健脾清化方、健脾清化方拆方(益气健脾方及清热化湿方)、尿毒清颗粒干预8周。测定用药后各组血清TC、TG、LDL、VLDL及肾组织TNF-α水平。结果模型组与正常组及假手术组比较,血清TC、TG、LDL、VLDL及肾组织TNF-α水平均显著升高(P均<0.01)。与模型组比较,健脾清化方组、清热化湿组、尿毒清组血清TC、TG、LDL、VLDL及肾组织TNF-α水平均显著降低(P均<0.01),益气健脾组血清TC、TG、VLDL均显著降低(P均<0.01),但LDL及肾组织TNF-α水平差异无统计学意义(P均>0.05)。结论健脾清化方可改善脂质代谢紊乱,并下调肾组织TNF-α的表达,从而改善肾脏炎症反应,实现抗肾纤维化的作用。方中的清热化湿药物对于降低LDL和肾组织TNF-α水平起着核心作用。

Objective To investigate the mechanism of “Jianpi Qinghua Decoction” （JQD） on renal fibrosis by observing the impact of JQD on serum total cholesterol （ TC）, triglyceride （ TG）, low-density lipo- protein （LDL）, very-low-density lipoprotein （VLDL）, and kidney tumor necrosis factor-α （TNF-α） expres- sions in focal segmental glomerulosclerosis rats induced by nephrectomy combined with adriamycin. Methods Totally 56 male SD rats were divided into normal group, sham operation group, model group, JQD group, Yiqi Jianpi group, Qingre Huashi group, and Niaoduqing group （ all n = 8） . The model of focal segmental glomeru- losclerosis was established by the unilateral nephrectomy and the injection of adriamycin in caudal vein of rat at a dose of 3 mg/kg in the latter 5 groups. JQD, the disassembled prescription of Jianpi Qinghua Decoction （ Yiqi Jianpi Decoction and Qingre Huashi Decoction ）, and Niaoduqing Capsule were administered separately for 8 weeks. The serum TC, TG, LDL, and VLDL levels and the expression of Kidney TNF-α were determined. Re- suits Compared with normal group and sham operation group, the serum TC, TG, LDL, and VLDL levels and the kidney TNF-α expression in the model group were significantly higher （all P 〈0. 01 ） . Compared with the model group, the JQD group, Qingre Huashi group, and Niaoduqing group had significantly lower serum TC, TG, LDL, and VLDL levels and kidney TNF-ct expression （ all P 〈 0. 01 ） . Compared with the model group, the Yiqi Jianpi group had significantly lower serum TC, TG, and VLDL levels （ all P 〈 0.01 ） , while the serum LDL level and kidney TNF-α expression remained unchanged （ all P 〉 0. 05 ） . Conclusions JQD can regulate serum lipids and lower the TNFα expression in kidney tissue and thus improve the renal inflammation and relieve renal fibrosis. The heat-clearing and dampness-removing herbs in the prescription play a central role in fighting a- gainst renal fibrosis.