小檗碱减轻慢性肾衰竭大鼠的肾脏损伤

Berberine attenuates renal injury in rats with chronic renal failure

目的探讨小檗碱(BBR)对慢性肾衰竭(CRF)大鼠的作用及可能的机制。方法将大鼠随机分为假手术(sham)组、慢性肾衰竭模型(model)组(切除5/6肾建立CRF大鼠模型)、小檗碱(BBR)治疗组、尿毒清颗粒(UCG)治疗组,每组10只。用全自动生化仪检测各组大鼠的肾功能指标;ELISA法检测MMP-2、MMP-9水平;PAS、Masson染色法观察肾组织纤维化程度;免疫组织化学方法检测肾脏组织中NF-κB p65、IL-6的表达;Western blot检测肾脏组织纤维化相关蛋白及TGF-β1/ERK信号通路蛋白的表达。结果与假手术组相比,模型组大鼠肾功能及肾组织病理学损害显著增加,BBR可以改善CRF大鼠的肾功能及肾组织病理学损害。与假手术组相比,模型组大鼠血清中MMP-2、MMP-9水平明显下降(P<0.05),IL-6、NF-κB p65表达上调(P<0.05),FN、α-SMA、Col-Ⅰ、Col-Ⅲ、TGF-β1、p-ERK1/2蛋白的表达水平均上调(P<0.05),而BBR治疗显著逆转了这些分子的表达(P<0.05)。结论BBR可能通过抑制TGF-β1/ERK1/2通路改善肾脏炎症和纤维化,发挥对CRF大鼠的保护作用。

Objective To investigate the effect of berberine(BBR)on chronic renal failure(CRF)rats and its mechanism.Methods CRF rat model was established by removing 5/6 kidneys and all rats were randomly divided into sham group,chronic renal failure model group,berberine treatment group and uremic clearance granules(UCG)treatment group with 10 in each.Renal function indexes in each group were examined by an automated biochemistry instrument.The level of MMP-2 and MMP-9 were detected by ELISA.The degree of renal fibrosis was observed by PAS and Masson staining microscopy.The expression of NF-κB p65 and IL-6 were detected by immunohistochemistry method.Expression of fibrosis-related proteins and TGF-β1/ERK signaling pathway proteins in renal tissues was detected by Western blot.Results Compared with sham group,renal function and renal histopathological damage was significantly increased in the model group,and BBR improved renal function and histopathological damage in CRF rats.Compared with the sham group,the serum level of MMP-2 and MMP-9 was significantly decreased(P<0.05),the expression of IL-6 and NF-κB p65 was up-regulated(P<0.05).The expression of FN,α-SMA,Col-Ⅰ,Col-Ⅲ,TGF-β1,and p-ERK1/2 proteins was up-regulated in the model group of rats(P<0.05),while the BBR treatment significantly reversed the expression of these molecules(P<0.05).Conclusions BBR may improve inflammation and fibrosis by inhibiting TGF-β1/ERK1/2 pathway,and play a protective role in the kidney of CRF rat.