主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2017, Vol. 40 ›› Issue (3): 219-225.doi: 10.3969/j.issn.1006-2157.2017.03.008

• 科技之窗 • 上一篇    下一篇

通络保肾复方对糖尿病大鼠肾脏内质网应激指标P-IRE1α、GRP78的影响*

张杰,李建民#,荣小龙,刘秀萍,周国民,韩雪,周雨,何华,宋越   

  1. 北京市中西医结合医院肾病科 北京 100039
  • 收稿日期:2016-09-28 出版日期:2017-03-30 发布日期:2017-03-30
  • 通讯作者: 李建民,男,博士,主任医师,研究方向:中医肾脏病治疗,E-mail:ljmh1128@vip.163.com
  • 作者简介:张杰,男,硕士,住院医师
  • 基金资助:
    *国家自然科学基金面上项目(No.81273706)

Influence of Tongluo Baoshen Fang on indexes of renal endoplasmic reticulum stress-P-IRE1α and GRP78 in rats with diabetes*

ZHANG Jie, LI Jianmin#, RONG Xiaolong, LIU Xiuping, ZHOU Guomin, HAN Xue, ZHOU Yu, HE Hua, SONG Yue   

  1. Department of Nephropathy, Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100039
  • Received:2016-09-28 Online:2017-03-30 Published:2017-03-30

摘要: 目的 探讨通络保肾复方及其拆方对链脲佐菌素(STZ)诱导糖尿病大鼠高血糖肾损伤内质网应激反应(ERS)启动因子P-IRE1α和分子伴侣GRP78的影响。方法 将雄性SD大鼠随机分成正常组和造模组。造模组大鼠采用腹腔注射STZ方法建立糖尿病大鼠模型。造模成功后将造模组大鼠随机分成模型对照组、缬沙坦组(8.93 mg/kg)、通络保肾复方组(19.43 g/kg)、通络保肾补虚组(6.92 g/kg)、通络保肾解毒组(12.5 g/kg)。观察各组大鼠日常活动的一般情况;应用免疫组化法及IPP软件半定量分析6周和16周各组大鼠p-IRE1α及GRP78的蛋白表达。结果 普通光镜下可见P-IRE1α、GRP78主要位于造模组大鼠肾脏近段、远端肾小管细胞及肾小球细胞的胞浆内;IPP免疫组化半定量法显示:6周和16周模型组与正常组大鼠相比较P-IRE1α、GRP78的蛋白表达增加(P<0.05);与模型组大鼠相比,6周和16周缬沙坦组、通络保肾复方组、通络保肾补虚组、通络保肾解毒组P-IRE1α、GRP78的蛋白表达减少(P<0.05),各治疗组之间无差别(P>0.05)。结论 糖尿病高血糖诱导肾损伤大鼠模型中存在内质网应激反应的激活;通络保肾复方及其拆方均可能通过抑制内质网应激而发挥肾脏保护作用;同时可推测糖尿病高血糖肾损伤的中医学核心病机是本虚标实。

关键词: 内质网应激, 糖尿病肾病, 通络保肾复方, 免疫组化, 大鼠

Abstract: Objective To discuss the influence of Tongluo Baoshen Fufang (TBF) and its disassembled formulas on P-IRE1α, promoter of endoplasmic reticulum stress (ERS) and GRP78, molecular chaperone, in diabetic rats with hyperglycemic kidney injury induced by streptozocin (STZ). Methods Male SD rats were randomly divided into normal group and modeling group. The model of diabetes was established by applying intraperitoneal injection of STZ in model group. After successfully modeling, the modeling group was randomly divided into model group, valsartan group(8.93 mg/kg), TBF group(19.43 g/kg), Tongluo Baoshen Buxu group (TBB group,6.92 g/kg) and Tongluo Baoshen Jiedu group (TBJ group,12.5 g/kg). The general conditions of rat daily activities were observed in all groups. The expressions of p-IRE1α and GRP78 were analyzed semi-quantitatively by using immunohistochemistry and IPP software after 6 weeks and 16 weeks. Results P-IRE1α and GRP78 mainly existed in the cytoplasm of proximal and distal renal tubule cells and glomerular cells observed by light microscope. The results of semi-quantitative immunohistochemistry and IPP software showed that the expressions of P-IRE1α and GRP78 increased in model group compared with normal group after 6 weeks and 16 weeks. Compared with model group, the expressions of P-IRE1α and GRP78 decreased in valsartan group, TBF group, TBB group and TBJ group (P<0.05) after 6 weeks and 16 weeks. The comparison among valsartan group, TBF group, TBB group and TBJ group did not show difference(P>0.05). Conclusion The rat model of kidney injury induced by hyperglycemia has ERS activation. TBF and its disassembled formulas can take play a renal protective role through inhibiting ERS. It can be speculated that the central pathogenesis of diabetic hyperglycemic kidney injury is deficiency of the root and excess of the tip in Chinese medicine.

Key words: endoplasmic reticulum stress, diabetic nephropathy, Tongluo Baoshen Fang, immunohistochemistry, rats

中图分类号: 

  • R285.5