小檗碱对糖尿病大鼠肾小管间质病变的作用及可能机制  

Effects and underlying mechanism of berberine on renal tubulointerstitial injury in diabetic rats

作　　者：马泽军[1] 胡绍兰[1] 王珊珊[1] 郭欣[1] 张晓娜[1] 孙蓓[1] 陈莉明[1] 

机构地区：[1]天津医科大学代谢病医院内分泌研究所卫生部激素与发育重点实验室天津市代谢性疾病重点实验室,300070

出　　处：《中华医学杂志》2016年第38期3072-3077,共6页National Medical Journal of China

基　　金：国家自然科学基金（81470187）

摘　　要：目的探讨小檗碱（BBR）对2型糖尿病（DM）大鼠肾小管间质病变的作用及其可能机制。方法30只6周龄清洁级雄性SD大鼠，按随机数字表法选取10只作为正常对照（NC）组，其余20只高脂喂养6周后，以链脲佐菌素（STZ）30 mg/kg尾静脉注射诱导糖尿病模型。造模成功的糖尿病大鼠随机分为DM组（10只）和BBR组（10只）。BBR组大鼠每天给予BBR 150 mg/kg灌胃，NC组和DM组每天给予等量生理盐水灌胃。灌胃8周后检测各组大鼠24 h尿微量白蛋白（mAlb）、尿N－乙酰－β－D氨基葡萄糖苷酶（NAG）、血糖和血脂水平；苏木精－伊红（HE）和马松（Masson）染色观察各组大鼠肾小管间质病理改变；免疫组化、实时定量PCR和Western印迹法观察各组大鼠肾组织E－钙黏素（E－cad）、α－平滑肌肌动蛋白（α－SMA）、核因子－κB（NF－κB）和单核细胞趋化蛋白1（MCP－1）的表达。结果干预8周后BBR组大鼠24 h尿mAlb[（170.5±58.1）比（253.7±53.0）mg]和NAG[（33.5±7.2）比（49.5±9.3）U/L]均低于DM组，差异均有统计学意义（均P〈0.05）。与DM组相比，BBR组大鼠肾小管间质病理学变化明显改善。与NC组相比，DM组大鼠肾组织E－cad的mRNA和蛋白表达下降，而α－SMA、NF－κB和MCP－1 mRNA和蛋白表达增加，差异均有统计学意义（均P〈0.05）；与DM组相比，BBR组大鼠肾组织E－cad mRNA和蛋白表达增加，α－SMA、NF－κB和MCP－1表达减少，差异均有统计学意义（均P〈0.05）。结论小檗碱能减轻糖尿病大鼠肾小管间质病变，该作用可能与减少肾脏NF－κB、MCP－1表达，进而抑制肾小管上皮细胞转分化有关。ObjectiveTo investigate the effect of Berberine on renal tubulointerstitial injury and its potential mechanism in rats with type 2 diabetes mellitus （T2DM）.MethodsThirty Sprague-Dawley rats were randomly divided into 3 groups： normal control rats （NC group）, diabetic rats without drug treatment （DM group）, diabetic rats treated with Berberine （BBR group） for 8 weeks. At the end of the study, blood and urine samples were collected for biochemical examination, and tubulointerstitial fibrosis was quantified by Hematoxylin and Eosin （HE） and Masson staining. The expressions of E-cadherin （E-cad）, α-smooth muscle actin （α-SMA）, nuclear factor-κB （NF-κB） and monocyte chemoattractant protein 1 （MCP-1） were detected by immunohistochemistry analysis, real-time polymerase chain reaction （RT-PCR） and Western blot analysis. Results24 h urinary microalbumin （mAlb）[（170.5±58.1） vs （253.7±53.0） mg]and urinary N-acetyl-glucosaminidase （NAG）[（33.5±7.2） vs （49.5±9.3）U/L]in diabetic rats were significantly decreased by BBR treatment（both P〈0.05）. The apparent renal tubulointerstitial injury was found in the DM group, which was ameliorated by BBR treatment. The expression of α-SMA, NF-κB and MCP-1 were significantly decreased, accompanied by increased expression of E-cad in BBR-treated DM rats （all P〈0.05）.ConclusionBBR could ameliorate renal tubulointerstitial injury in diabetic rats, the mechanism of which may be associated with the amelioration of epithelial-mesenchymal transition （EMT） through suppressing the expression of the NF-κB and MCP-1.

关 键 词：糖尿病 2型 肾疾病 小檗碱 肾小管间质病变 

分 类 号：R259[医药卫生—中西医结合]