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火绒草黄芪混煎液对系膜增生性肾小球肾炎模型大鼠的改善作

          用及机制          Δ


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          侯 侠 ,赵 玥 ,张 颖 ,贾 冬 ,仲 坤 ,房小楠 ,董笑博 ,齐 越 (1.江苏省徐州医药高等职业学校药
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          学技术系,江苏 徐州 221116;2.辽宁中医药大学附属第二医院药理室,沈阳 110034;3.辽宁中医药大学中医
          研究生学院,沈阳 110847)
          中图分类号 R965          文献标志码     A      文章编号 1001-0408(2022)19-2359-05
          DOI  10.6039/j.issn.1001-0408.2022.19.11
          摘  要 目的 研究火绒草黄芪混煎液(HRCHQ)对系膜增生性肾小球肾炎(MsPGN)模型大鼠的改善作用及机制。方法 将70只
          大鼠按体质量分为假手术组(n=10)和造模组(n=60)。假手术组大鼠行假手术,造模组大鼠采用免疫学方法(弗氏佐剂+牛血清
          蛋白+脂多糖)复制MsPGN模型。将造模成功的50只大鼠按体质量随机分为模型组和HRCHQ 高、中、低剂量组(4.05、2.03、1.02
          g/kg)以及盐酸贝那普利片组(20 mg/kg),每组各 10 只。假手术组、模型组大鼠灌胃蒸馏水,其余各组大鼠灌胃相应药液 15
          mL/kg,每天1次,连续5周。末次给药后,测定大鼠血清中总蛋白、白蛋白、尿素氮含量,采用免疫组织化学染色法检测大鼠肾脏
          组织中转移生长因子β1 (TGF-β1 )、肿瘤坏死因子α(TNF-α)的表达,采用免疫荧光法检测大鼠肾脏组织中补体C3的表达,采用West‐
          ern blot法检测大鼠肾脏组织中磷脂酰肌醇3激酶/蛋白激酶B/糖原合酶激酶3β(PI3K/Akt/GSK3β)信号通路相关蛋白的磷酸化水
          平及纤连蛋白(FN)的表达水平。结果 与模型组比较,HRCHQ高剂量组大鼠血清中总蛋白、白蛋白含量均显著升高(P<0.05或
          P<0.01);血清中尿素氮含量,肾脏组织中TGF-β1、TNF-α、FN、补体C3表达水平和PI3K、Akt、GSK3β蛋白的磷酸化水平均显著降
          低(P<0.05或P<0.01)。结论 HRCHQ可通过减少系膜细胞增殖以及抑制PI3K/Akt/GSK3β信号通路活性来改善MsPGN。
          关键词 火绒草;黄芪;系膜增生性肾小球肾炎;系膜细胞;磷脂酰肌醇3激酶/蛋白激酶B/糖原合酶激酶3β信号通路

          Improvement   effects  of  Huorongcaohuangqi    admixture   decoction  on   mesangial   proliferative
          glomerulonephritis model rats and its mechanism
          HOU Xia ,ZHAO Yue ,ZHANG Ying ,JIA Dong ,ZHONG Kun ,FANG Xiaonan ,DONG Xiaobo ,QI Yue             1
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         (1. Dept. of Pharmaceutical Technology,Jiangsu Provincial Xuzhou Pharmaceutical Vocational College,Jiangsu
          Xuzhou 221116,China;2. Dept. of Pharmacology,the Second Affiliated Hospital of Liaoning University of TCM,
          Shenyang 110034,China;3. College of Graduate School,Liaoning University of Traditional Chinese Medicine,
          Shenyang 110847,China)
          ABSTRACT   OBJECTIVE To study the improvement effects of Huorongcaohuangqi (HRCHQ) admixture decoction on
          mesangial proliferative glomerulonephritis(MsPGN)model rats and its mechanism. METHODS Totally 70 rats were divided into
          sham operation group(n=10)and modeling group(n=60)according to body weight. Sham operation group underwent sham
          operation,and MsPGN model was induced by immunological method(Freund’s adjuvant+BSA+lipopolysaccharide)in modeling
          group. After successfully modeling,50 rats were randomly divided into model group,HRCHQ high-dose,medium-dose and low-
          dose groups (4.05,2.03,1.02 g/kg),Benazepril hydrochloride tablet group (20 mg/kg),with 10 rats in each group. Sham
          operation group and model group were given distilled water intragastrically; other groups were given relevant medicine
          intragastrically 15 mL/kg,once a day,for consecutive 5 weeks. After last administration,the contents of total protein,albumin and
          urea nitrogen were determined in the serum of rats. The expressions of transforming growth factor β1(TGF-β1 )and tumor necrosis
          factor α(TNF-α)in renal tissue were detected by immunohistochemistry;the expression of complement C3 in renal tissue was
          detected by immunofluorescence. The phosphorylation level of phosphatidylinositol 3 kinase/protein kinase B/glycogen synthase
          kinase 3β(PI3K/Akt/GSK-3β) signal pathway related proteins and expression level of fibronectin (FN) in renal tissue were
                                                             detected by Western blot. RESULTS Compared with model
             Δ 基金项目 国家重大新药创制中药新品种研发及其关键创新技
                                                             group,the serum contents of total protein and albumin were
          术项目(No.2017ZX09301019);辽宁省科技厅课题(No.2019-ZD-0843,
                                                             increased significantly in HRCHQ high-dose group (P<0.05
          No.2021-BS-046)
                                                             or P<0.01). The serum content of urea nitrogen, the
             *第一作者 副教授,硕士。研究方向:中药新药药理、神经药理。
          E-mail:Houxia_75@163.com                           expressions of TGF-β1,TNF-α,FN and complement C3,and
             # 通信作者 教授,博士。研究方向:中药新药药理、神经药理。E-                the phosphorylation levels of PI3K,Akt and GSK3β protein
          mail:lnzyxyqy2003@163.com                          were all decreased significantly (P<0.05 or P<0.01).


          中国药房    2022年第33卷第19期                                            China Pharmacy 2022 Vol. 33 No. 19  ·2359·
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