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indexes(WBC,RBC,PLT),liver function indexes(TP,ALB,AST,ALT),blood lipid indexes(TC,TG,HDL-C,LDL-C),
        the contents of glucose(GLU),urea nitrogen(BUN)and serum creatinine(Scr)were detected in each group. Uranyl acetate-lead
        citrate staining was used to observe ultrastructural changes of renal tissue. Immunohistochemical method was used to detect the
        protein expression of TGF-β 1 and HPA-1 in renal tissue. RESULTS:Compared with blank control group,in the model control
        group,the glomerular podocytes were widely fused or disappeared,microvilli were formed,basement membrane was heavily
        thickened,a large number of electron dense substance was deposited under the epithelium,TGF-β 1 and HPA-1 positive cells were
        significantly increased;24 h UTP,PLT,the contents of TC,TG and HDL-C,the percentage of TGF-β 1 and HPA-1 positive cells
        were increased significantly,while RBC,the contents of TP and ALB were decreased significantly (P<0.05 or P<0.01).
        Compared with model control group,above ultrastructural changes of administration groups were improved to different extents,and
        TGF-β 1 and HPA-1 positive cells were decreased. The 24 h UTP,the percentage of TGF-β 1 positive cells(except for SZD low-dose
        group),WBC(except for SZD alone groups and combination groups),PLT and TC content(except for TPT group),TG content
        (except for SZD low-dose alone and its combination group),the percentage of HPA-1 positive cells were decreased significantly;
        the percentage of TGF-β 1 positive cells in SZD high-dose+TPT group as well as the percentage of HPA-1 positive cells in SZD+TPT
        groups were significantly lower than TPT group. RBC and GLU content(except for SZD low-dose group and TPT group),TP and
        ALB content(except for SZD low-dose group)were increased significantly,while the content of GLU in SZD high-dose+TPT
        group was significantly higher than TPT tablets group (P<0.05 or P<0.01). CONCLUSIONS:SZD combined with TPT can
        relieve myelosuppression caused by TPT,reduce proteinuria of MN model rats and improve pathological damage of renal tissue in
        rats. Its mechanism is related to the down-regulation of protein expression of TGF-β 1 and HPA-1,and the reduction of TC and TG
        content in the blood.
        KEYWORDS     Membranous nephropathy;Shenqi zhilong decoction;Tripterygium polyglycoside tablets;Blood routine indexes;
        Liver function;Blood lipid;TGF-β1;HPA-1;Rat


            膜性肾病(MN)是临床上常见的肾小球疾病之一,                         骨髓抑制亦有所减轻。鉴于此,本研究通过建立MN大
        多以肾病综合征的形式起病,根据发病原因可分为原发                            鼠模型,观察参芪蛭龙汤联合雷公藤多苷片对大鼠血常
        性膜性肾病(IMN)和继发性膜性肾病(SMN),其中IMN                       规、血糖、血脂、肝肾功能、尿蛋白、肾组织超微结构、乙
                                  [1]
        患者约占MN患者总数的75% 。研究表明,近年来MN                          酰肝素酶1(HPA-1)、转化生长因子β 1 (TGF-β 1 )等指标的
                                            [2]
        的发生率逐年上升,可能与环境污染有关 。目前,MN                           影响,探讨参芪蛭龙汤对雷公藤多苷片的增效减毒作用
        的西医治疗以糖皮质激素联合免疫抑制剂为主,上述疗                            及可能机制,旨在为临床联合用药提供理论依据。
        法虽有一定的疗效,但伴有明显的副作用(如股骨头坏                            1 材料
        死、高血压、糖尿病、严重感染、肝肾毒性等),且停药后                          1.1  仪器
        容易复发    [2-3] 。                                         XS-500i 型全自动血液分析仪[希森美康医用电子
            参芪蛭龙汤是黑龙江省中医药科学院肾病科治疗                          (上海)有限公司];7600-020 型全自动生化分析仪、
        MN 的特色医院制剂,由党参、黄芪、当归、川芎等 10 味                       H-7650型透射电子显微镜(日本Hitachi公司);DM6B型
        药材组成,临床使用十余年,疗效较好,具有一定的新药                           荧光正置显微镜、RM2235 型石蜡切片机(德国 Leica 公
                 [3]
        开发价值 。雷公藤(Tripterygium wilfordii Hook. f.)为         司);KQ-600DE 型超声仪(昆山市超声仪器有限公司);
        卫矛科雷公藤属木质藤本植物,具杀虫、消炎、解毒之功                           H-2050R型超速冷冻离心机(湖南湘仪实验室仪器开发
        效 [4-5] 。雷公藤多苷是从雷公藤根木质部中提取所得的                       有限公司)。
        化合物 。现代药理研究表明,雷公藤多苷具有抑制免                            1.2 药品与试剂
               [6]
        疫细胞活化、修复免疫复合物介导的足细胞损伤、减少                                参芪蛭龙汤组方药材党参、黄芪、当归、川芎、水蛭、
        蛋白尿的作用 。多项研究表明,以雷公藤多苷为主要                            地龙、僵蚕、虎杖、淫羊藿、凤尾草的饮片均由黑龙江中
                     [7]
        成分的雷公藤多苷片具有较好的缓解蛋白尿的作用                      [8-10] ;  医药大学附属第一医院提供,经黑龙江中医药大学基础
        但该药具有骨髓抑制、肝功能损害、性腺抑制等副作用,                           医学院田明教授鉴定均为真品。
        使得其临床应用受到了限制             [5,11] 。本课题组在临床实践              雷公藤多苷片(浙江得恩德制药股份有限公司,
        中发现,参芪蛭龙汤在缓解MN患者水肿等症状方面的                            批号:1901113B,规格:10 mg);阳离子牛血清白蛋白
        效果较好,但在降低尿蛋白方面却起效较慢;雷公藤多                           (C-BSA)冻干粉(美国Chondrex公司,批号:190538);不
        苷片具有较好的降低尿蛋白作用,但存在明显的骨髓抑                            完全弗氏佐剂(美国Sigma公司,批号:SLBQ2284V);白
        制;而二药联合应用后,既能明显降低 MN 患者尿蛋白                          蛋白(ALB)、总蛋白(TP)、血肌酐(Scr)、尿素氮(BUN)、
        水平,又能改善其水肿症状,同时雷公藤多苷片所致的                            葡萄糖(GLU)、胆固醇(TC)、三酰甘油(TG)、高密度脂


        ·1576  ·  China Pharmacy 2020 Vol. 31 No. 13                                中国药房    2020年第31卷第13期
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