复方血竭合剂治疗大鼠系膜增生性肾小球肾炎的实验研究

目的:观察复方血竭合剂对系膜增生性肾小球肾炎(MsPGN)模型大鼠的治疗作用.方法:根据文献方法制作MsPGN动物模型,观察复方血竭合剂对其肾脏损伤有关指标的作用.结果:复方血竭合剂可明显降低模型大鼠肾小球肿瘤坏死因子-α(TNF-α)的活性.结论:复方血竭合剂能抑制系膜细胞(MC)增生,减少系膜基质的积聚,其作用可能与其抑制肾小球分泌TNF-α有关.     

肾炎康对大鼠系膜增生性肾炎MCP-1的影响

目的:探讨中药肾炎康对大鼠系膜增生性肾炎(MsPGN)模型病理及尿中单核细胞趋化蛋白-1(MCP-1)的影响。方法:采用大鼠慢性血清病性MsPGN模型。于造模第6周随机分为肾炎康组及模型组,肾炎康组每日灌服肾炎康3ml,模型组每日灌服等量自来水。42天后,观察两组大鼠尿MCP-1及尿蛋白水平,BUN、Scr及肾脏病理改变。结果:模型组尿MCP-1、尿蛋白量、BUN及Scr均显著高于正常对照组(P均<0.01)。病理检查见肾小球肿大,系膜细胞及基质弥漫性增殖,肾小球内及肾间质炎性细胞浸润。肾炎康组尿MCP-1、尿蛋白、BUN及Scr虽亦高于对照组(P<0.05～0.01),但显著低于模型组(P<0.05～0.01)。肾脏病理改变明显比模型组轻,系膜轻度或节段增殖,炎性细胞浸润轻。结论:肾炎康能减轻MsPGN系膜细胞增殖及炎症细胞浸润,减轻病理改变,改善肾功能,降低尿中MCP-1及尿蛋白,因而对MsPGN有治疗作用,其机制可能与抑制MCP-1有关。     

健脾利水活血方对系膜增殖性肾小球肾炎大鼠生化指标的影响

目的探讨健脾利水活血方治疗系膜增殖性肾小球肾炎 (mesangialproliferativeglomerulonephritis,MsPGN)的作用机制。方法参照文献制作MsPGN大鼠模型 ,观察健脾利水活血方对大鼠血液流变学(hemorheology)、血浆低密度脂蛋白 (lowdensitylipoprotein ,LDL)及白蛋白 (albumin)的影响。结果与模型组比较 ,经健脾利水活血方治疗后 ,大鼠血浆LDL明显降低 ,白蛋白明显升高 ,血液黏度明显降低 (P <0 .0 5 ,P <0 .0 1)。结论健脾利水活血方可能是通过调节LDL抑制系膜细胞 (mesangialcell,MC)产生过多的细胞外基质 (extracellularmatrix ,ECM) ,从而达到治疗MsPGN的作用。     

大黄对增生性肾小球肾炎大鼠肾小球细胞外基质的影响

研究大黄对增生性肾小球肾炎大鼠肾小球细胞外基质主要成分－纤维连接素的影响,方法：运用大鼠肾毒血清性肾为作为增生性肾小球肾炎的模型,观察大黄治疗后纤维连接率的变化及其对系膜区面积的影响。结果：大黄可显著抑制纤维连接素的产生,抑制肾小球系膜区的扩张,结论：大黄通过抑制细胞外基质增生延缓了增生性肾小球肾炎的进行性发展,保护了肾功能。     

白芍总苷对大鼠系膜增生性肾小球肾炎的保护作用

目的观察白芍总苷（TGP）对大鼠系膜增生性肾小球肾炎（MsPGN）的保护作用，为TGP治疗MsPGN提供实验依据。方法采用胃肠道综合免疫方法建立大鼠MsPGN模型，以不同剂量的TGP干预，以雷公藤多苷为对照，观察TGP对大鼠蛋白尿、血生化指标以及肾组织形态学改变的影响。结果模型组大鼠尿蛋白增加，血肌酐和尿素氮升高，血浆总蛋白和白蛋白下降，模型组的肾小球系膜细胞中至重度增生，系膜基质聚积。灌胃给予TGP干预4周后，给药组的系膜细胞增生、基质聚积减少，大鼠的蛋白尿减轻，血肌酐和尿素氮下降。结论TGP可保护MsPGN大鼠的肾功能，部分逆转受损的肾小球病理改变。     

肾疏宁对系膜增生性肾炎模型大鼠肾小球固有细胞表型转化的影响

目的:观察肾疏宁对系膜增生性肾炎(MsPGN)模型大鼠肾小球系膜细胞(MC)表型转化的作用,探讨肾疏宁防治肾小球硬化的作用机制。方法:在建立MsPGN大鼠模型基础上,延长造模时间至12～16周,使其向肾小球硬化进展,观察肾疏宁对肾小球α平滑肌肌动蛋白(α-SMA)表达的影响,并设苯那普利为阳性对照组。结果:12、16周末造模各组α-SMA表达量明显高于正常组(P<0.01)。16周末肾疏宁组α-SMA表达量明显优于苯那普利组(P<0.01)。结论:肾疏宁能抑制MC表型转化,减少肾小球内固有细胞α-SMA的表达,可能是防治肾小球硬化的部分作用机制。     

三黄汤水提物ZY-4对大鼠系膜增生性肾小球肾炎的影响

【目的】观察三黄汤水提物ZY-4对大鼠系膜增生性肾小球肾炎的影响。【方法】选用SD大鼠,复制大鼠系膜增生性肾小球肾炎模型,将造模成功大鼠随机分成模型组与ZY-4组(剂量为20 mg·kg-1·d-1),另设正常对照组。检测各组大鼠尿蛋白浓度、24 h尿蛋白量、肾功能以及形态结构的变化。【结果】正常组大鼠各项检测指标均正常。模型组大鼠尿蛋白浓度和24h尿蛋白总量均显著升高(P0.05);肾组织光镜检查显示系膜细胞增生明显,系膜基质增多;肾组织超微结构检查显示足突肿胀、融合,系膜区尚有电子致密物沉积。ZY-4组尿蛋白浓度和24 h尿蛋白总量显著降低,与模型组比较差异均有统计学意义(P0.05);光镜检查显示系膜细胞轻度增生,基质增多不明显,细胞数略有增加;肾组织超微结构检查显示系膜增生较模型组轻,足突融合不明显,未见电子致密物沉积。【结论】ZY-4对大鼠系膜增生性肾小球肾炎具有一定治疗作用。     

系膜增生性肾炎大鼠肾小球周期素激酶抑制剂P27的变化及意义

目的:探讨周期素激酶抑制剂P27在系膜增生性肾炎模型Thy1肾炎大鼠系膜细胞(MC)增生中的作用.方法:利用抗胸腺细胞抗体制成Thy1肾炎模型,Western印迹法测定肾小球裂解液P27蛋白水平, RT-PCR方法测定肾小球P27 mRNA,ELISA方法测定肾小球裂解液细胞外基质(ECM)蛋白(纤维连接蛋白及Ⅳ型胶原).结果:Thy1肾炎第1天P27水平即有明显下降,第3天(MC增生最为明显)P27水平最低,第5天(MC增生开始消散)P27水平有所回升,提示P27水平与MC增生程度有关;Thy1肾炎第3天肾小球P27 mRNA与正常对照组比较无明显差别;而Thy1肾炎大鼠肾小球纤维连接蛋白和Ⅳ型胶原均升高(P<0.01),在第3天达峰值,第5天略有回降,但仍显著高于正常对照组(P<0.01).结论:P27水平下降可能在Thy1肾炎MC增生中起重要作用.     

咪唑立宾对急性肾炎大鼠肾小球系膜区Ⅳ型胶原的影响

目的探讨咪唑立宾对急性Thy1肾炎大鼠肾小球系膜区Ⅳ型胶原(COL4)的影响。方法将81只雄性Wistar大鼠随机分为对照组、模型组和咪唑立宾组,每组27只。第5天,比较3组大鼠24 h尿蛋白定量,采用PAS染色评估3组大鼠肾小球系膜区细胞外基质(ECM)增殖情况,采用PCR检测3组大鼠肾小球系膜区COL4 mRNA表达水平,采用Western blot检测3组大鼠肾小球系膜区COL4蛋白表达水平。结果对照组大鼠平均24 h尿蛋白定量、肾小球系膜区基质与肾小球面积比值(ECM/GA)、系膜区COL4 mRNA表达水平、系膜区COL4蛋白表达水平均低于模型组和咪唑立宾组,咪唑立宾组以上各指标均低于模型组,差异有统计学意义(均P<0.05)。结论咪唑立宾抑制系膜增生的机制可能是下调COL4 mRNA及蛋白的表达。     

肾系康及其拆方组治疗系膜增生性肾炎血尿的实验研究

目的:在临床证实肾系康治疗系膜增生性肾炎血尿具有明显疗效基础上,试图通过系膜增生性肾炎动物模型验证其疗效,并明确各不同拆方亚组的作用强弱及协同,以指导临床应用。方法:用刘震报道的方法加以改进建立大鼠MsPGN模型,并检测各组大鼠尿液中红细胞数以判定治疗结果。结果:肾系康及滋阴、活血组能够减少MsPGN大鼠尿红细胞数。结论:肾系康对MsPGN血尿有显著疗效,方中滋阴活血药起主要作用,临床治疗血尿可加大用量。     

Effect of Colquhoumia Root on the Expression of Transforming Growth a Root on the Expression of Transforming Growth Factor-β in Mesangial Proliferation Glomerulonephritis Model

To study the efficacy and the mechanism of Colquhoumia root (Tripterygium hypoglaucum (Le,vL)Hutch) in the treatment of mesangial proliferation glomerulonephritis (MsPGN), SD rats were injected with anti-thymocyte serum (ATS) to make MsPGN model (anti-Thy1 model). The rats were then divided into 3 groups: normal control group, anti-Thy1 model group and treatment group. Histopathological (HE, PAS), immunohistochemical, RT-PCR technique and computer imaging analysis system were used to evaluate mesangial matrix production, the expression of TGF-β1 protein and mRNA in the tissues of kidney.Our result showed that proteinuria and the ratio of extracellular matrix/glomerular capillaries area (ECM/CA) were increased significantly in model group. The expression of both TGF-β1 protein and mRNA in glomeruli was much higher in model group than in control group (P<0.01). After the treatment with Colquhoumia root, proteinuria, ECM/CA and the expression of both TGF-β1 protein and mRNA in glomeruli were significantly decreased in treatment group as compared with those in model group. It is concluded that Colquhoumia root is effective in reducing proteinuria and mesangial matrix proliferation in MsPGN and it may achieve these effects by inhibiting the expressions of TGF-β1 protein and mRNA of mesangial cells.     

Effect of Coiquhoumia Root on the Expression of Transforming Growth Factor-β in Mesangiai Proliferation Giomerulonephritis Model

Summary： To study the efficacy and the mechanism of Colquhoumia root （ Tripterygium hypoglaucure （Le,vL） Hutch） in the treatment of mesangial proliferation glomerulonephritis （MsPGN）, SD rats were injected with anti-thymoeyte serum （ATS） to make MsPGN model （anti-Thyl model）. The rats were then divided into 3 groups： normal control group, anti-Thyl model group and treatment group. Histopathologieal （HE, PAS）, immunohistoehemieal, RT-PCR technique and computer imaging analysis system were used to evaluate mesangial matrix production, the expression of TGF-β protein and mRNA in the tissues of kidney. Our result showed that proteinuria and the ratio of extraeellular matrix/glomerular capillaries area （ECM/CA） were increased significantly in model group. The expression of both TGF-β protein and mRNA in glomeruli was much higher in model group than in control group （P〈0.01）. After the treatment with Colquhoumia root, proteinuria, ECM/CA and the expression of both TGF-β1 protein and mRNA in glomeruli were significantly decreased in treatment group as compared with those in model group. It is concluded that Colquhoumia root is effective in reducing proteinuria and mesangial matrix proliferation in MsPGN and it may achieve these effects by inhibiting the expressions of TGF-β1 protein and mRNA of mesangial cells.     

Quantitative Analysis of Glomeruli Lesions in Patients with Mesangial Proliferative Glomerulonephritis

ＱｕａｎｔｉｔａｔｉｖｅＡｎａｌｙｓｉｓｏｆＧｌｏｍｅｒｕｌｉＬｅｓｉｏｎｓｉｎＰａｔｉｅｎｔｓｗｉｔｈＭｅｓａｎｇｉａｌＰｒｏｌｉｆｅｒａｔｉｖｅ　ＧｌｏｍｅｒｕｌｏｎｅｐｈｒｉｔｉｓＳＵＮＪｉａｎｐｉｎｇ（孙建平）；ＷＡＮＧＹｕｎｑｉｎ（王韵琴）...     

内皮素反义寡核苷酸在抑制大鼠肾小球系膜细胞和系膜基质增生中的 …

OBJECTIVE: To investigate the effect of endothelin-1 (ET-1) on mesangial cells(MC) proliferation and mesangial matrix expansion in vivo. METHODS: Antisense oligodeoxynucleotide(As-ODN) and its control sequences, sense oligodeoxynucleotide(Se-ODN) and mismatch oligodeoxynucleotide(Mis-ODN), targeting pre-proendothelin-1 mRNA (ppET-1) were delivered into the kidney of rats with mesangioproliferative glomerulonephritis (MsPGN) model respectively at day 2 by lipofectin-mediated gene transfer method. The efficiency of transfer of ODNs into MC was examined with biotinylated As-ODN staining. Four days after the rats were sacrificed, the influence of ODNs on ET-1 production by glomeruli was tested with radioimmunoassay(RIA). The action of ODNs on MC proliferation and mesangial matrix expansion was evaluated with quantitative pathologic analysis. RESULTS: ODNs were transferred into MC in vivo. The glomerular ET-1 production was decreased by As-ODN [(32 +/- 19) ng/g, P < 0.05] with reduction of mesangial cell proliferation [(0.82 +/- 0.04)/100 micron 2, P < 0.05] and mesangial matrix expansion[(12.8 +/- 1.6)%, P < 0.05], where Se-ODN and Mis-ODN did not show any effect on all of these. CONCLUSIONS: Specific inhibition of ET-1 gene expression leads to reduction of proliferation of mesangial cell and expansion of mesangial matrix in rats with MsPGN model. ET-1 is one of the important inflammatory mediators which can stimulate MC proliferation and mesangial matrix expansion in vivo.     

糖皮质激素联合白芍总苷对大鼠系膜增生性肾炎的治疗作用

目的观察糖皮质激素联合白芍总苷(TGP)对大鼠系膜增生性肾小球肾炎(MsPGN)的治疗作用。方法采用胃肠道综合免疫方法建立大鼠MsPGN模型,以强的松为对照,观察激素和TGP联合应用对大鼠蛋白尿、血生化指标以及肾组织形态学改变的影响。蛋白尿采用双缩脲法测定,血生化指标由半自动生化分析仪测定,肾组织形态学为普通光镜观察。结果模型组大鼠出现大量蛋白尿,血肌酐(Cre)、尿素氮(Bun)、转氨酶(ALT)和甘油三酯(TG)升高,血浆总蛋白(TP)和白蛋白(Alb)下降,模型组的肾小球系膜细胞中至重度增生,系膜基质聚积。灌胃给予强的松和TGP(1mg/kg 100mg/kg)联合治疗4周后,肾小球系膜细胞增生、基质聚积明显减少,大鼠的蛋白尿减轻,Cre、Bun、ALT和TG下降,TP和Alb上升,与单独使用TGP(100mg/kg)、强的松(5mg/kg)有类似作用。结论TGP与强的松联用,可降低强的松的用量,对于MsPGN大鼠的肝肾功能有明显改善作用,并能部分逆转受损肾小球的病理改变。     

商陆皂甙甲治疗大鼠抗-Thy1.1系膜增生性肾炎的实验研究

目的　观察商陆皂甙甲 (Es A)对 Wistar大鼠抗 - Thy1.1系膜增生性肾炎模型的治疗效果。方法　制备鼠抗 - Thy1.1系膜增生性肾炎模型 ,随机分为 Es A治疗组、地塞米松 (DXM)治疗组、未治疗组 (模型组 )。另设正常对照组。观察 Es A、DXM治疗 7d后大鼠血清尿素氮、肌酐、2 4 h尿蛋白定量及肾组织病理变化。结果　所有模型大鼠与正常对照组比较 ,尿蛋白定量升高、有核细胞计数增多及系膜区面积扩张均具显著性差异 (P<0 .0 0 1～0 .0 5 ) ;Es A、DXM治疗组与未治疗组比较 ,尿蛋白定量降低、有核细胞计数减少及系膜区面积减小具显著性差异(P<0 .0 0 1～ 0 .0 1)。结论　 Es A对大鼠抗 - Thy1.1肾炎有减少尿蛋白排泄、抑制肾小球系膜细胞及系膜基质增生、改善肾脏病理损害的作用     

火把花根和泼尼松对大鼠系膜增殖性肾炎的研究

目的应用火把花根（昆明山海棠）及泼尼松对MsPGN大鼠模型干预，并探讨其作用机制。方法将MsPGN大鼠模型，分成模型对照组、模型治疗组（火把花根及泼尼松），并设空白组对照。每1，2及4周末测24h尿蛋白，处死大鼠各5只，留取肾脏，观察肾脏病理并用RT—PCK及免疫组化方法检测肾组织中MCP-1的mRNA及蛋白质表达。结果MsPGN模型组大鼠尿蛋白、肾小球病理及肾组织内MCP-1的mRNA及蛋白质表达较空白组均显著上调（P〈0．01）。火把彳劬圾泼尼松干预后，上述上调指标均被抑制（P〈0．01）。结论火把花根和泼尼松对MsPGN大鼠模型干预的效果较好，此疗效可能与下调肾组织MCP-1相关。两药可能有协同作用。     

实验用2型糖尿病大鼠模型及其肾病观察

目的研究高脂高糖喂养加小剂量链脲佐菌素诱导的2型糖尿病大鼠模型的可行性及其肾病特点。方法SD大鼠高脂高糖喂养8周后,腹腔注射STZ(35mg/kg)诱导糖尿病大鼠,观察血糖,空腹胰岛素,血脂,肾功能,并行光镜及电镜观察肾脏结构改变。结果高脂高糖喂养加小剂量STZ诱导的糖尿病大鼠的体重,血糖,血脂较对照组明显增高,胰岛素敏感指数下降。糖尿病12周时,肾肥大指数、尿微量白蛋白、尿素氮、肌酐、肾小球截面计、基质面积、基质面积比均较正常对照组升高,而毛细血管面积比下降。结论高脂高糖喂养加小剂量STZ诱导的糖尿病大鼠符合2型糖尿病发病特点及糖尿病肾病病理改变。     

参地颗粒对系膜增生性肾小球肾炎大鼠血清和肾脏MMP-9/TIMP-1的影响

目的 探究参地颗粒治疗系膜增生性肾小球肾炎（mesangial proliferative glomerulonephritis,MsPGN）的机制.方法 采用改良慢性血清病法复制MsPGN模型.将37只SD大鼠随机分为空白组（n=10）、模型组（n=8）、贝那普利组（n=9）和参地颗粒组（n=10）.常规生化法检测24 h尿蛋白定量（24-hour urinary protein,24hUP）,酶联免疫吸附法测定血清纤维连接蛋白（fibronectin,FN）、Ⅳ型胶原（collagen-Ⅳ,Col-Ⅳ）、基质金属蛋白酶9（matrix metalloproteinase-9,MMP-9）和金属蛋白酶组织抑制剂-1（tissue inhibitor of metalloproteinase-1,TIMP-1）水平,光镜下观察肾脏组织病理学变化,采用免疫组织化学法检测大鼠肾组织MMP-9和TIMP-1蛋白表达水平.结果 与模型组比较,参地颗粒组和贝那普利组大鼠24hUP水平,血清FN、Col-Ⅳ水平,以及肾小球基质相对面积显著降低（P＜0.05）;参地颗粒组血清和肾组织MMP-9水平显著升高（P＜0.05）,TIMP-1水平显著降低（P＜0.05）,血清MMP-9/TIMP-1比值显著升高（P＜0.05）.给药4周和8周后,参地颗粒组24hUP均显著低于贝那普利组（P＜0.05）,血清和肾组织MMP-9/TIMP-1比值显著高于贝那普利组（P＜0.05）.结论 参地颗粒可以降低MsPGN大鼠24hUP,降低肾脏细胞外基质含量,其机制可能与上调体内MMP-9水平、下调TIMP-1水平及升高MMP-9/TIMP-1比值有关.