小檗碱通过Toll样受体减轻高脂诱导的大鼠肾损害

Berberine alleviate the renal damage induced by high fat diet and it may ralated to the toll-like receptors

目的:探讨小檗碱减轻高脂诱导肾脏损害与Toll样受体的相关性。方法:50只雄性Wistar大鼠随机均分为正常喂养组(NF组)、正常喂养小檗碱组(NF+LBBR组)、高脂喂养安慰剂组(HF组)、高脂喂养低剂量小檗碱组(HF+LBBR组)和高脂喂养高剂量小檗碱组(HF+HBBR组)。前两组正常喂养8周,其余3组高脂喂养8周;喂养4周后,NF+LBBR组、HF+LBBR组和HF+HBBR组分别予不同浓度的小檗碱干预,其余2组予等量溶剂干预。干预结束后,取血标本、肾脏组织,测定代谢及肾功能指标。采用单因素方差(ANOVA)分析各组间指标的差异。相关危险因素分析采用Pearson法和logistic回归分析法。结果:HF组大鼠的体质量、游离脂肪酸(FFA)、空腹血糖(GLU)、空腹胰岛素(FINS)、尿微量白蛋白(MAU)、尿白蛋白/肌酐(ACR)、白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)、IL-6的水平明显升高(P<0.05),肾脏发生损害。与HF组相比,HF+LBBR组和HF+HBBR组上述指标水平降低(P<0.05),肾脏损害改善。Pearson相关分析显示,ACR与GLU(r=0.35)、FINS(r=0.82)、FFA(r=0.49)、IL-1(r=0.77)、TNF-α(r=0.78)、IL-6(r=0.76)正相关(P<0.05)。logistic多因素回归分析显示,IL-6与ACR独立相关[OR=1.18,95%CI 1.03～1.35,P=0.014]。HF组大鼠肾脏组织Toll样受体4(TLR4)、TLR2的表达减少,核转录因子-κB(NF-κB)、转化生长因子-β(TGF-β)表达增加(P<0.05);给予小檗碱后,这一趋势被逆转(P<0.05)。结论:小檗碱能改善高脂喂养大鼠肾脏损伤,这可能与小檗碱提高大鼠肾脏组织Toll样受体(TLR4、TLR2)的表达水平有关。

Objective:To investigate the effects of berberine on the alleviation of the renal damage induced by high fat diet and its correlation with toll-like receptors.Methods:Fifty male Wistar rats were randomly divided into the five groups.The normal feeding group(NF group),the normal feeding and berberine treatment group(NF+BBR group),the high-fat feeding group(HF group),the high-fat feeding and low-dose berberine treatment group(HF+LBBR group),and high-fat feeding and high-dose berberine treatment group(HF+HBBR group).Except the two normal feeding group,the rats in other three groups were fed with high-fat diet for8weeks.After4week,the three berberine intervention groups received different concentrations of berberine,respectively.At the end of the experiment,the blood samples and kidney tissue were taken to analyze the metabolism and renal function indicators.The single factor analyses of variance(ANOVA)was used to compare differences between groups.The relevant risk factors were analyzed by Pearson correlation test and logistic regression.Results:The weight,and levels of free fatty acids(FFA),fasting glucose(GLU),fasting insulin(FINS),microalbumin(MAU),microalbumin/uric creatinine(ACR),interleukin-1(IL-1),tumor necrosis factor-α(TNF-α),and IL-6in HF group were higher than those in NF group(P<0.05).The above indexes in HF+LBBR group and HF+HBBR group were lower than those in HF group(P<0.05).Renal pathology revealed kidney damage in HF group,while kidney damage was improved in HF+LBBR and HF+HBBR groups.Pearson correlation analysis showed that ACR was positively correlated with blood glucose(r=0.35),insulin(r=0.82),free fatty acids(r=0.49),IL-1(r=0.77),TNF-α(r=0.78),and IL-6(r=0.76,P<0.05).Logistic regression analysis showed that IL-6was independent risk factor for ACR(OR=1.18,95%CI1.03-1.35,P=0.014).In kidney tissue of HF group,the TLR4and TLR2expressions were significantly decreased,while nuclear factor-κB(NF-κB)and transforming growth factor-β(TGF-β)expressions were increased(P<0.05),and berberine reversed the changes(P<0.05).Conclusions:The berberine could alleviated kidney damage of high-fat feeding rats,which might be related to berberine increased toll-like receptors(TLR4,TLR2)expressions in kidney tissue.