大鼠抗GBM肾炎模型的建立及不同病期的生化指标和肾组织病理学观察

目的：为研究人类新月体抗肾炎的发病机制，建立大鼠抗肾小球基底膜（BGM）肾炎的动物模型，方法：提取S－D大鼠GBM抗原，将此抗原免疫新西兰白兔获得抗血清，再将此抗血清从尾静脉一次性注射给S－D大鼠。实验分2组：肾炎模型组及正常对照组。定期于第4天、第14天第第21天检测大鼠24h尿蛋白，血肌酐及血尿素的含量和肾组织病理学改变。结果：大鼠肾炎模型组：大鼠注射抗血清后于第4天出现大量蛋白尿，第14天血肌酐，血尿素显著升高，并持续上升，肾组织病理表现为肾小球内细胞数明显增加，大量新月体形成及蛋白管型，GBM呈不规则增厚，足突融合，内皮细胞脱落，坏死，免疫荧光检查见IgG、鼠IgG沿GBM线形分布，大鼠正常对照组以上指标均无明显改变。结论：通过动态观察大鼠抗GBM肾炎的病变变化，证实该模型病变与人类新月体性肾炎的病变较为一致，该模型可用于探讨人类新月体体肾炎的实验研究。     

201A中药合剂对大鼠抗肾小球基底膜肾炎免疫功能的影响

目的 观察201A中药合剂防治大鼠抗肾小球基底膜(GBM)肾炎的疗效。方法 建立大鼠抗GBM肾炎模型。实验分3组：201A处理组、肾炎对照组及正常对照组。201A处理组大鼠一次性尾静脉注射抗GBM抗血清后即刻给予201A合剂(0．42g／kg，灌胃)，肾炎对照组大鼠一次性尾静脉注射抗GBM抗血清后则给予等量的生理盐水，均至第21天。定期于第4、14和21天，检测大鼠尿蛋白，并收集血标本检测T淋巴细胞转化功能、血清中循环免疫复合物及抗GBM自身抗体。结果 肾炎对照组大鼠注射抗血清后第4天即出现异常蛋白尿，T淋巴细胞转化功能明显高于正常，并于第14天血中检测到高滴度的抗GBM自身抗体；而201A处理组鼠上述病变均明显好转。结论 201A中药合剂能够改善大鼠抗GBM肾炎的肾功能。     

20lA中药合剂对大鼠抗肾小球基底膜肾炎病变的影响

目的 观察201A中药合剂防治大鼠抗肾小球基底膜(GBM)肾炎的疗效。方法 建立大鼠抗GBM肾炎模型。实验分3组：201A处理组、肾炎对照组及正常对照组。201A处理组大鼠一次性尾静脉注射抗GBM抗血清后即刻给予201A合剂(0．42g／kg，灌胃)，至第21天。对照组则给予等量的生理盐水。定期于第4天、第14天和第21天，检测大鼠尿蛋白，观察肾组织病理学改变。结果 肾炎对照组大鼠注射抗血清后于第4天即出现异常蛋白尿，肾小球内可见细胞数增加和新月体形成，肾小管内大量蛋白管型，GBM呈不规则增厚。而201A处理组鼠上述病变均明显好转。结论 201A能够明显改善抗肾小球基底膜肾炎大鼠的肾功能。     

201A中药合剂对大鼠抗肾小球基底膜肾炎病变的影响

目的　观察 2 0 1A中药合剂防治大鼠抗肾小球基底膜 (GBM)肾炎的疗效。方法　建立大鼠抗GBM肾炎模型。实验分 3组 :2 0 1A处理组、肾炎对照组及正常对照组。 2 0 1A处理组大鼠一次性尾静脉注射抗GBM抗血清后即刻给予 2 0 1A合剂 (0 .42g/kg ,灌胃 ) ,至第 2 1天。对照组则给予等量的生理盐水。定期于第 4天、第 14天和第 2 1天 ,检测大鼠尿蛋白 ,观察肾组织病理学改变。结果　肾炎对照组大鼠注射抗血清后于第 4天即出现异常蛋白尿 ,肾小球内可见细胞数增加和新月体形成 ,肾小管内大量蛋白管型 ,GBM呈不规则增厚。而 2 0 1A处理组鼠上述病变均明显好转。结论　 2 0 1A能够明显改善抗肾小球基底膜肾炎大鼠的肾功能     

兔抗鼠胸腺细胞抗血清的制备及应用

目的 应用大鼠胸腺细胞悬液免疫新西兰大白兔，制备兔抗大鼠胸腺细胞抗血清(ATS)。方法 初次免疫采用大鼠胸腺细胞悬液与福氏完全佐剂乳化混合后作为免疫原液，于大白兔皮下多点注射；加强免疫分别采取静脉注射和皮下多点注射的方法。并用间接免疫荧光的方法对抗血清效价进行测定。结果 皮下加静脉注射免疫法制得ATS效价达1：2000，皮下注射免疫法制得ATS效价为1：1000。结论 两种免疫方法均可诱导产生满意的ATS。高效价的ATS为系膜增殖性肾炎动物模型的研究提供了方法学基础。     

异搏停,山莨菪碱对大鼠被动型Heymann肾炎病变的影响

应用大鼠肾小管上皮抗原（Ｔｕｂ－Ａｇ）的抗血清制做大鼠被动型Ｈｅｙｍｎｎ肾炎（ＰＨＮ）动物模型，并选用钙通道阻滞剂（ＣＣＢ）一异搏停和山莨菪碱进行处理，观察两药对其病变的影响。结果异搏停组及山莨菪碱组大鼠尿蛋白均明显低于ＰＨＮ模型组，病理组织损伤亦有一定程度的改善。提示：上述两药对大鼠ＰＨＮ病变有治疗作用。     

肝素抑制大鼠Thy—1肾炎病变的实验研究

经连续４次大鼠性静脉注射免抗大鼠ｔｈｙ－１抗血清，建立大鼠ｔｈｙ－１系膜增生性肾上球肾炎模型。与此同时注射肝系，通过肾小球细胞计数，增殖细胞核抗原阳性细胞数及α－平滑肌肌动蛋白免疫酶标染以，以观察肝素对肾小球系膜细胞增生的影响；用过碘酸六胺银和Ⅳ型胶原免疫酶标染色观察肝素对肾小球系膜基质的作用。     

大鼠抗胸腺细胞血清性肾炎早期凋亡病变的观察

目的:研究大鼠系膜增生性肾炎,即抗胸腺细胞血清性肾炎(ATSN)早期凋亡的病变。方法:利用兔抗大鼠胸腺细胞抗血清(ATS)复制大鼠ATSN模型,实验40 min、24 h和7 d分别取各组大鼠肾皮质切片用末端转移酶介导的duTP缺口末端标记(Tunel)技术和电镜检查方法观察其肾小球系膜细胞(MC)早期凋亡病变。结果:实验40 min,ATSN大鼠出现明显的肾小球MC胞核染色质固缩,聚集于核膜呈现边缘化改变,核膜多处凸起。肾小球系膜区细胞Tunel染色呈阳性,荧光强度均可达+++～++++。结论:ATSN发病早期(1 h内),肾小球MC可发生凋亡,随着时间的延长,逐渐出现MC溶解。     

肝素抑制大鼠Thy-1肾炎病变的实验研究

经连续4次大鼠尾静脉注射免抗大鼠thy－1抗血清（ATS），建立大鼠thy－1系膜增生性肾小球肾炎模型。与此同时注射肝素，通过肾小球细胞计数、增殖细胞核抗原（PCNA）阳性细胞数及a一平滑肌肌动蛋白（a－SMA）免疫酶标染色，以观察肝素对肾小球系膜细胞增生的影响；用过碘酸六胺银（PASM）和Ⅳ型胶原（ColⅣ）免疫酶标染色观察肝素对肾小球系膜基质的作用。结果发现肝素组与正常组之间，上述指标均受到明显的抑制，提示肝素对大鼠thy—1至肾炎有良好的治疗效果。     

大鼠原位免疫复合物型肾炎模型的建立

一般利用阳离子化牛血清白蛋白建立原位免疫复合物肾炎模型多用家兔。作者用大鼠,参照伊藤Bartsford方法,成功地建立了大鼠原位免疫复合物肾炎模型。     

抗RAP抗体对肾小球上皮足突细胞RAP基因表达调控

目的：研究抗ＲＡＰ抗体对肾小球上皮足突细胞ＲＡＰ基因表达调控。方法：受体相关蛋白（ＲＡＰ）多抗，作用于体外分离培养的ＳＤ大鼠肾小球上皮足突细胞１２小时，以模拟Ｈｅｙｍａｎｎ肾炎（ＨＮ）模型体内循环抗体作用于肾小球发病过程，采用ＲＴ－ＰＣＲ半定量分析的方法研究肾小球足突细胞受体相关蛋白基因表达。结果：ＲＡＰ多抗作用于培养肾小球上皮足突细胞使得细胞ＲＡＰ基因表达增高。结论：ＲＡＰ循环抗体调控肾小球上皮     

抗基底膜性肾小球肾炎的实验研究

对肾毒性血清诱发的大白鼠抗基底膜性肾小球肾炎进行动态观察。光镜下肾小球内细胞数目明显增多。12h内兔抗鼠IgG呈线型分布于鼠肾小球基底膜上。鼠抗兔IgG抗体在7天内产生并沉积于肾脏。电镜下肾小球病变在3周内逐渐加重,并可见电子致密物沉积于肾小球基底膜与内皮细胞之间或肾小球基底膜内。鼠的抗基底膜性肾小球肾炎诱发率高,其病变与人类某些肾炎相似。     

Childhood Henoch-Sch?nlein purpura nephritis and IgA nephropathy: one disease entity?--A clinico-pathologically comparative study.

In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Sch?nlein purpura nephritis (HSPN), 31 children with IgA nephropathy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and follow-up study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8% children with IgA nephropathy, but only 10% in HSPN (P < 0.05). The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59% had gastrointestinal symptoms and 47% suffered from arthralgia, compared with only abdominal pain in 3.2% children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5% of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9% of IgA nephropathy and 6.3% of HSPN, but endothelial proliferation in 65.6% of HSPN and 29% of IgA nephropathy (all P < 0.01). Thin basement membrane nephropathy was only found in 6.5% children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2% of HSPN, and overwhelming IgG deposits in 12.5% of HSPN with relatively weak IgA deposits, moreover 6.3% of HSPN showed linear IgG deposits in glomerular capillary. Totally 71.9% of HSPN had IgG deposits in glomeruli and only 19.4% of IgA nephropathy showed glomerular IgG deposits (P < 0.01). No IgG deposit was observed in 81.6% of IgA nephropathy, among them most showed IgA and IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG deposits couldn't be found in IgA nephropathy. Mean 20 months follow-up showed complete remission in 72.5% of HSPN, but only 19.4% in IgA nephropathy after 34 months follow-up. Moreover, 64.5% of IgA nephropathy had consistent hematuria and proteinuria and 16.1% had active nephritides (P < 0.05). It was concluded that significant clinico-pathological difference was found between HSPN and IgA nephropathy, which didn't support the one disease entity hypothesis. HSPN and IgA nephropathy are probably two diseases with similar immune abnormalities.     

Childhood Henoch-Sch(o)nlein Purpura Nephritis and IgA Nephropathy:One Disease Entity?--A Clinico-pathologically Comparative Study

In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schonlein purpura nephritis (HSPN), 31 children with IgA nephropathy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8 %children with IgA nephropathy, but only 10 % in HSPN (P＜0.05). The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59 % had gastrointestinal symptoms and 47 % suffered from arthralgia,compared with only abdominal pain in 3.2 % children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5 % of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9 % of IgA nephropathy and 6.3 % of HSPN, but endothelial proliferation in 65.6% of HSPN and 29 % of IgA nephropathy (all P＜0.01). Thin basement membrane nephropathy was only found in 6.5 % children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2 %of HSPN, and overwhelming IgG deposits in 12.5 % of HSPN with relatively weak IgA deposits,moreover 6.3 % of HSPN showed linear IgG deposits in glomerular capillary. Totally 71.9 % of HSPN had IgG deposits in glomeruli and only 19.4 % of IgA nephropathy showed glomerular IgG deposits (P＜0.01). No IgG deposit was observed in 81.6 % of IgA nephropathy, among them most showed IgA and IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG deposits couldn't be found in IgA nephropathy. Mean 20 months follow-up showed complete remission in 72.5 % of HSPN, but only 19.4 % in IgA nephropathy after 34 months follow-up. Moreover, 64.5 % of IgA nephropathy had consistent hematuria and proteinuria and 16.1% had active nephritides (P＜0.05). It was concluded that significant clinico-pathological difference was found between HSPN and IgA nephropathy, which didn't support the one disease entity hypothesis.HSPN and IgA nephropathy are probably two diseases with similar immune abnormalities.     

Childhood Henoch-Schönlein purpura nephritis and IgA nephropathy: one disease entity?

Summary In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Sch?nlein purpura nephritis (HSPN), 31 children with IgA nephropathy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8% children with IgA nephropathy, but only 10% in HSPN (P<0.05). The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59% had gastrointestinal symptoms and 47% suffered from arthralgia, compared with only abdominal pain in 3.2% children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5% of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9% of IgA nephropathy and 6.3% of HSPN, but endothelial proliferation in 65.6% of HSPN and 29% of IgA nephropathy (allP<0.01). Thin basement membrane nephropathy was only found in 6.5% children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, loose and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2% of HSPN, and overwhelming IgG deposits in 12.5% of HSPN with relatively weak IgA deposits, moreover 6.3% of HSPN showed linear IgG deposits in glomerular capillary. Totally 71.9% of HSPN had IgG deposits in glomeruli and only 19.4% of IgA nephropathy showed glomerular IgG deposits (P<0.01). No IgG deposit was observed in 81.6% of IgA nephropathy, among them most showed IgA and IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG deposits couldn't be found in IgA nephropathy. Mean 20 months follow-up showed complete remission in 72.5% of HSPN, but only 19.4% in IgA nephropathy after 34 months follow-up. Moreover, 64.5% of IgA nephropathy had consistent hematuria and proteinuria and 16.1% had active nephritides (P<0.05). It was concluded that significant clinico-pathological difference was found between HSPN and IgA nephropathy, which didn't support the one disease entity hypothesis. HSPN and IgA nephropathy are probably two diseases with similar immune abnormalities. ZHOU Jianhua, male, born in 1964, Professor     

东菱迪芙治疗大白兔抗肾小球基底膜肾炎的实验研究

目的：观察应用东菱迪芙(DF—521）治疗大白兔抗肾小球基底膜(GBM)肾炎的疗效。方法：建立大白兔自相期抗GBM肾炎模型；实验分两组：DF—521治疗组和末治疗组(对照组)。大白兔注射肾毒血清后6h内开始静脉给药，对照组仅给等量的生理盐水。定期观察一般情况，并测定尿蛋白、血肌酐、血纤维蛋白原的水平，2周后宰杀大白兔，观察肾组织病理改变。结果：药物治疗后大白兔尿蛋白水平，纤维家沉积数、新月体数及肾小球细胞总数较肾炎对照组显著减少6肾质量和血肌酐水平无显著差别。结论：东菱迪芙能够改善抗GBM肾炎大白兔的肾脏病变，疗效显著。     

复制大鼠膜性肾小球肾炎伴新月体形成和肾小球硬化模型的研究

ＳｐｒａｇｕｅＤａｗｌｅｙ大鼠预免疫２周后,采用由腹腔逐渐过渡至静脉的方法,每日注射阳离子化牛血清白蛋白（ＣＢＳＡ）。结果：静脉注射ＣＢＳＡ２周后,荧光显微镜观察显示ＩｇＧ沿肾小球毛细血管壁呈颗粒状沉积,光镜下可见有新月体形成,电镜下可见大量上皮下电子致密沉积物;４周后,上皮下电子致密沉积物融合成大片状;６周后,较多大鼠出现肾小球硬化。     

实验性原位性肾炎的药物防治研究

本文用抑制TxA_2合成酶的药物——苄基咪唑(BIm)和抑制血小板聚集的活血化瘀中药藏红花、毛冬青甲素和丹参对实验性原位性肾炎模型进行了干扰,结果显示BIm,藏红花和毛冬青甲素组动物的尿蛋白显著低于对照组,肾小球中的免疫复合物吸收加速,病理组织损害亦较对照组有显著的改善,尿毒症的死亡率较对照组减少。但丹参组和对照组比较则无显著性差别。结论;藏红花、毛冬青甲素和BIm对实验性原位性肾炎有治疗作用。提示血小板和TxA_2在原位性肾炎发病机理和病情发展中起着重要的致病作用。     

低分子肝素对兔抗肾小球基底膜肾炎的疗效观察

目的　观察低分子肝素 (LMWH)对兔抗肾小球基底膜 (GBM)肾炎的疗效。方法　建立兔抗GBM肾炎模型 ;实验分两组 :LMWH治疗组和对照组。LMWH治疗组注射肾毒血清后 6h内开始给药 ,对照组仅给等量的生理盐水。定期观察一般情况 ,并测定尿蛋白、血肌酐水平 ,2周后宰杀兔 ,观察肾组织病理改变。结果　LMWH组尿蛋白、纤维素沉积数、新月体数、肾小球细胞总数、肾小管间质损伤指数、炎细胞浸润数均较对照组显著减少。结论　低分子肝素可显著改善抗GBM肾炎兔的肾脏病变。     

来氟米特对大鼠肾毒血清性肾炎早期肾损害的保护作用

目的探讨来氟米特（LEF）对大鼠肾毒血清性肾炎早期肾损害的保护作用。方法建立大鼠肾毒血清肾炎模型,随机分为正常对照组、病理对照组、LEF干预组（5mg／kg／d,灌胃）。2周末检测24h尿蛋白含量、血清学指标;观察肾小球病理形态及免疫组化变化。结果病理对照组24h尿蛋白水平明显高于正常对照组（P〈0．01）,血浆白蛋白水平明显低于正常对照组（P〈0．05）,肾小球内细胞数、含新月体肾小球数、硬化肾小球数、肾组织中MCP-1、ED1^＋细胞浸润明显高于正常对照组（P〈0．05）。肾组织中ED1^＋细胞数与尿蛋白排泄量、形成新月体的肾小球百分数呈显著正相关（P〈0．01）,形成新月体的肾小球百分数与尿蛋白排泄量亦呈显著正相关（P〈0．01）。LEF干预组大鼠尿蛋白水平、肾小球细胞总数、硬化肾小球数、新月体数、肾小球ED1^＋细胞浸润及MCP-1表达均明显低于病理对照组（P〈0．01,0．05）。结论LEF能改善肾毒血清性肾炎大鼠早期肾脏病变,其机制可能部分与抑制肾组织MCP-1表达和巨噬细胞浸润有关。