培哚普利对实验性糖尿病大鼠肾脏的保护作用

观察培哚普利（ｐｅｒｉｎｄｏｐｒｉｌ）对链脲霉素诱导的糖尿病（ＤＭ）大鼠肾脏的保护作用。ＤＭ对照组（ＤＣ组）每日注射长效胰岛素，ＤＭ治疗组（ＤＰ组）并每天给予培哚普利１ｍｇ／ｋｇ。于病程１、３、６个月测２４小时尿蛋白。取肾脏作光镜和电镜检查，测定肾小球平均截面积（ＭＧＰＡ）和肾小球平均体积（ＭＧＶ）。结果显示６个月期间ＤＣ、ＤＰ组尿蛋白定量明显高于ＮＣ组（Ｐ＜０．０１），且ＤＣ组高于ＤＰ组（Ｐ＜０．０５）。３、６个月时ＤＣ、ＤＰ组ＭＧＰＡ、ＭＧＶ均大于ＮＣ组，６个月时ＤＰ组小于ＤＣ组。电镜观察表明，ＤＭ大鼠系膜区扩张，足突融合，基底膜增厚等，但ＤＰ改变较轻。提示ＤＭ大鼠存在肾脏结构和功能异常；培哚普利对肾脏有保护作用。     

大黄对糖尿病大鼠肾小球形态改变的影响及定量分析

用先进的图像分析系统，观察了中药大黄提取物Ⅰ号对链脲菌素（ＳＴＺ）所致糖尿病肾病大鼠模型肾小球形态学的影响，结果提示，在病程第三天糖尿病组大鼠肾小球干均体积较大黄提取物Ⅰ号治疗组大鼠明显增大（Ｐ＜０．０１）；病程的第三、七和第１４天糖尿病组大鼠肾小球系膜区平均面积较治疗组扩大，有统计学差异（分别为Ｐ＜０．０１．Ｐ＜０．０１和Ｐ＜０．００１）．本研究在实验性大鼠的体内进一步证实大黄提取物Ⅰ号抑制肾脏肥大的作用。     

内皮素-1及其mRNA在早期糖尿病大鼠肾组织中的含量及其意义

目的探讨内皮素１及其ｍＲＮＡ在早期实验性糖尿病大鼠肾脏中的含量和意义。方法采用免疫组织化学、原位杂交技术检测糖尿病大鼠肾组织中ＥＴ１及其ｍＲＮＡ。结果ＥＴ１及ＥＴ１ｍＲＮＡ分布一致,主要分布于肾小球内皮细胞、系膜细胞、血管平滑肌细胞及肾小管上皮细胞之中,髓质高于皮质,二者在糖尿病发生后１～２周肾小球内均明显减少（Ｐ＜０．０５）,４周时开始增加（Ｐ＜０．０５）,而在髓质中则持续增加。结论ＥＴ１参与了早期实验性糖尿病大鼠肾小球高灌注及肾小管间质损     

福辛普利对糖尿病大鼠肾脏损伤的保护作用

目的探讨福辛普利对糖尿病大鼠肾脏损伤的保护机制。方法制备大鼠糖尿病模型并分别给予不同剂量福辛普利灌胃。12周后检测血糖、血清肌酐、肾重指数,观察肾小球体积、肾小球基底膜变化,测定肾小球平均截面积（MGA）和肾小球平均体积（MGV）。结果DM组及不同剂量福辛普利组间血糖、血清肌酐均无统计学差异;与DM组相比,5mg·kg^-1·d^-1组肾重指数降低（P〈0．05）,10mg·kg^-1·d^-1组肾重指数明显降低（P〈0．01）,各福辛普利组MGA和MGV均缩小（P均〈0．01）。结论早期应用福辛普利在一定程度上可减轻糖尿病大鼠肾脏的损伤。     

一氧化氮和内皮素与早期糖尿病大鼠肾小球高滤过的关系

目的　探讨一氧化氮（ Ｎ Ｏ） 和内皮素（ Ｅ Ｔ） 在早期糖尿病大鼠肾小球高滤过中的作用。方法采用链脲佐菌素（ Ｓ Ｔ Ｚ） 诱导的大鼠糖尿病模型，将糖尿病形成７ ～１４ 天定为早期，观察早期肾脏病变和血浆、组织匀浆中的硝酸盐（ Ｎ Ｏ３ ） 及内皮素水平变化。结果　糖尿病形成早期，肾重／ 体重增加（ Ｐ＜ ０ ．０５） ；且出现大量蛋白尿（ Ｐ＜ ０ ．００１） ；肌酐清除率（ Ｃ Ｃｒ） 明显增高（ Ｐ＜ ０ ．００１） ；血浆及组织匀浆中 Ｎ Ｏ３ 明显增高（ Ｐ＜ ０ ．００５） ，均与 Ｃ Ｃｒ 呈正相关关系；血浆及组织匀浆中 Ｅ Ｔ 水平明显下降（ Ｐ＜ ０ ．００１） 。结论　提示糖尿病早期已有肾脏病变； Ｃ Ｃｒ 升高间接表明肾小球滤过率（ Ｇ Ｆ Ｒ） 升高，研究结果认为 Ｎ Ｏ 是影响糖尿病早期肾小球高滤过的重要介质，而 Ｎ Ｏ 与 Ｅ Ｔ 又可能构成一对具有拮抗效应的血管活性物质，在早期糖尿病鼠肾小球高滤过中起重要的调控作用。     

速避凝对糖尿病大鼠肾脏表皮生长因子的干预作用

近年来认为糖尿病肾病（ＤＮ）早期实质上是多种细胞因子、生长因子和激素对高血糖的综合反应［１］。临床和实验表明：肾小球内皮细胞及基底膜上硫酸肝素糖蛋白（ＨＳＰＧ）成分的耗竭也是ＤＮ主要原因之一［２］。本实验通过观察低分子肝素（速避凝）治疗前后糖尿病大鼠肾功能以及肾内表皮生长因子（ＥＧＦ）表达的变化,以探讨速避凝对ＤＮ肾脏保护作用的可能机制。１　材料和方法１．１　动物模型的建立和分组　雄性ＳＤ大鼠４８只,体重１６０～１８０ｇ（购自上海实验动物中心）。在２％戊巴比妥麻醉下行左肾切除术。术后２周大鼠一般…     

低分子量肝素对增殖性肾炎的疗效观察

为观察低分子量肝素对增殖性肾炎的治疗作用，对４１例经肾活检证实组织学改变都有明显的系膜细胞增殖，并有不同程度硬化和肾小球内凝血的患者，按年龄、病程、临床表现及肾组织病变程度随机分为两组。对照组用激素、环磷酰胺和洛汀新；观察组在上述药物治疗基础上每日一次皮下注射低分子量肝素速避凝３０７５～６１５０ＩＵＡＸａ。结果表明，用低分子量肝素治疗组患者治疗４周后尿蛋白明显减少，血清白蛋白明显增高，总胆固醇下降，其中尿蛋白和血清白蛋白的变化与对照组比较差异有显著性（Ｐ＜０．０５）。虽然４周时各组治疗前后及两组间肌酐清除率变化差异无显著性，但８周及１２周时，两组间肌酐清除率差值的比较具有显著性意义（Ｐ＜０．０５），观察组肌酐清降率呈上升趋势。本研究提示低分子量肝素可使具有肾小球内凝血和硬化的增殖性肾炎患者尿蛋白减少，有利于肾病综合征早期缓解，而且出血危险性小，无需特别监护，便于长期应用。     

苯那普利对糖尿病大鼠肾组织细胞周期蛋白激酶抑制剂P21~(CIPI)蛋白表达的影响

目的：探讨苯那普利对糖尿病大鼠肾组织细胞周期蛋白激酶抑制剂Ｐ２１ ＣＩＰ１ 蛋白表达的影响。　方法：大鼠随机分单侧肾切除对照组（Ｃ 组） 、糖尿病组（ Ｄ 组） 及糖尿病苯那普利治疗组（ ＤＢ 组） 。１ 周后，应用免疫印迹（ Ｗｅｓｔｅｒｎ 杂交） 分析各组肾皮质Ｐ２１ＣＩＰＩ蛋白表达。血浆、肾皮、髓质血管紧张素转换酶（ＡＣＥ） 活性由荧光分光光度法测得。　结果：单侧肾切除糖尿病大鼠１ 周体重即明显下降（ Ｐ＜ ０－０５） ，肾重／ 体重即肾脏肥大指数却明显增加（ Ｐ＜ ０－０５） ，血浆ＡＣＥ 活性有所下降而肾皮质ＡＣＥ 活性却有所上升。Ｗｅｓｔｅｒｎ 杂交分析表明对照组肾皮质几乎没有Ｐ２１ＣＩＰ１ 蛋白表达，然而，糖尿病肾皮质Ｐ２１ ＣＩＰ１ 蛋白表达明显增加；苯那普利治疗１ 周对肾脏肥大有明显的抑制作用，对血浆、肾皮、髓质ＡＣＥ 活性抑制分别达８９－０ ％ 、７０－０ ％ 、７０－５ ％ ，对肾皮质Ｐ２１ ＣＩＰＩ蛋白表达抑制达６０－０ ％ 。结论：苯那普利对糖尿病肾脏肥大的抑制作用至少部分与Ｐ２１ ＣＩＰＩ蛋白表达降低有关，其确切机制尚有待于进一步研究     

糖尿病大鼠肾脏一氧化氮系统基因表达的研究

目的 研究糖尿病大鼠肾脏一氧化氮系统基因的表达。方法 观察了１２周ＳＴＺ－糖尿病大鼠肾脏皮质一氧化氮（ＮＯ）含量及一氧化氮合成酶（ＮＯＳ）活力,并应用ＲＴ－ＰＣＲ技术检测了肾脏皮质诱生型一氧化氮合成酶ｍＲＮＡ水平的改变。结果 糖尿病大鼠肾脏皮质ＮＯＳ活性及ｉＮＯＳ ｍＲＮＡ水平明显高于正常对照组（Ｐ〈０．０５）,然而ＮＯ含量却反而下降（Ｐ〈０．０５）。结论 糖尿病大鼠肾脏一氧化氮合成障碍,灭活加速     

伊贝沙坦对糖尿病大鼠一氧化氮系统及肾脏的影响

目的　研究伊贝沙坦对糖尿病大鼠一氧化氮 (NO)系统及肾脏的影响。　方法　随机将 4 0只Wistar大鼠分为 4组 ,每组 10只 ,分别为正常对照组、糖尿病组、伊贝沙坦组和开搏通组。病程 12周时处死大鼠 ,取血、尿和肾脏标本 ,测定尿量、体重、肾重 /体重比值、血糖、糖化血红蛋白(HbA1c) ;测定血清、尿液和肾组织的NO水平 ,通过免疫组化方法 ,检测肾脏组织诱导型一氧化氮合酶 (iNOS)蛋白的合成 ,并通过光镜和电镜观察肾脏的病理结构变化。　结果　治疗 12周后 ,糖尿病各组大鼠的尿量、肾重 /体重比值、血糖、HbA1c、血清、尿液和肾脏组织的NO水平、肾脏组织iNOS蛋白的合成、肾小球体积和肾小球基底膜厚度明显高于或大于正常组 ,体重明显低于正常组 (P <0 .0 1) ;伊贝沙坦组大鼠的血清、尿液和肾脏组织的NO水平、肾脏组织iNOS蛋白的合成、肾小球体积和肾小球基底膜厚度比糖尿病组明显减少 (P <0 .0 5 ) ;血清、尿液和肾组织NO水平与肾小球体积和肾小球基底膜厚度呈正相关。　结论　伊贝沙坦能延缓糖尿病大鼠肾脏功能损害的进展 ,其机制可能与伊贝沙坦不同程度地抑制糖尿病大鼠NO的产生有关。     

Glomerular basement membrane thickening in streptozotocin diabetic rats despite treatment with an aldose reductase inhibitor

This study concerns the possible prevention of glomerular basement membrane thickening in experimental diabetes by an aldose reductase inhibitor (ARI), Statil^®. ARI added to the chow was given to streptozotocin diabetic rats over a period of 6 months. Reference groups were control rats and diabetic rats on the same chow without ARI. The diabetic rats were given insulin two or three times a week, and blood glucose was measured monthly before insulin injections. There was a marked difference in the occurrence of cataracts between the two diabetic groups. ARI treated rats tended to have lower blood glucose than the diabetic reference group, but the difference was not significant. At the termination of the experiment, the left kidney was perfusion fixed, weighed, and prepared for light and electron microscopy. Systematic random sampling from the entire kidney was performed to obtain light microscopic visual fields and ultrathin sections from two glomeruli. Mean glomerular volume was estimated by light microscopy, and glomerular basement membrane thickness, by electron microscopy. Basement membrane thickness was significantly increased in untreated diabetic rats (174 nm, SD = 4.5 nm) as compared to that of controls (Mean: 154 nm, SD = 11.0 nm), and was even more so in ARI treated rats (187 nm, SD = 18.7 nm,) although the ARI treated rats showed less renal and glomerular hypertrophy than did untreated diabetic rats. In conclusion, the ARI treatment over an experimental period of 6 months attenuated diabetic renal and glomerular hypertrophy, but had no effect at all on diabetic glomerular basement membrane thickening.     

Novel biphenyl compound, VMNS2e, ameliorates streptozotocin-induced diabetic nephropathy in rats

Aim: To study the effect of a new biphenyl synthetic compound showing interactions with the active site of protein tyrosine phosphatase 1B by docking and molecular dynamics, VMNS2e in streptozotocin‐induced diabetic nephropathy in rats with various renal function parameters and renal ultrastructure. Methods: Streptozotocin (55 mg/kg)‐induced diabetic rats were orally treated once daily with VMNS2e (30, 60, and 120 mg/kg) for 8 weeks. The body weight and blood glucose levels of the rats were recorded during the study period. After 8 weeks of treatment creatinine clearance, urinary protein, blood urea nitrogen, urinary albumin excretion rate, and insulin levels were measured. An ultrastructure study of the kidney tissue was performed and the glomerular basement membrane thickness was measured. Results: Eight weeks of VMNS2e treatment significantly reduced the fasting blood glucose level, attenuated elevating blood urea nitrogen levels, and reduced glomerular basement membrane thickness. Conclusion: It is concluded that VMNS2e treatment at 30 and 60 mg/kg, when given for 8 weeks, partly ameliorated early diabetic nephropathy in diabetic rats.     

Selective proteinuria in diabetic nephropathy in the rat is associated with a relative decrease in glomerular basement membrane heparan sulphate

Summary In the present study we investigated whether glomerular hyperfiltration and albuminuria in streptozotocin-induced diabetic nephropathy in male Wistar-Münich rats are associated with changes in the heparan sulphate content of the glomerular basement membrane. Rats with a diabetes mellitus duration of 8 months, treated with low doses of insulin, showed a significant increase in glomerular filtration rate (p<0.01) and effective renal plasma flow (p<0.05), without alterations in filtration fraction or mean arterial blood pressure. Diabetic rats developed progressive albuminuria (at 7 months, diabetic rats (D): 42±13 vs control rats (C): 0.5±0.2 mg/ 24 h, p<0.002) and a decrease of the selectivity index (clearance IgG/clearance albumin) of the proteinuria (at 7 months, D: 0.20±0.04 vs C: 0.39±0.17, p<0.05), suggesting loss of glomerular basement membrane charge. Light- and electron microscopy demonstrated a moderate increase of mesangial matrix and thickening of the glomerular basement membrane in the diabetic rats. Immunohistochemically an increase of laminin, collagen III and IV staining was observed in the mesangium and in the glomerular basement membrane, without alterations in glomerular basement membrane staining of heparan sulphate proteoglycan core protein or heparan sulphate. Giomerular basement membrane heparan sulphate content, quantitated in individual glomerular extracts by a new inhibition ELISA using a specific anti-glomerular basement membrane heparan sulphate monoclonal antibody (JM403), was not altered (median (range) D: 314 (152–941) vs C: 262 (244–467) ng heparan sulphate/mg glomerulus). However, the amount of glomerular 4-hydroxyproline, as a measure for collagen content, was significantly increased (D: 1665 (712–2014) vs C: 672 (515–1208) ng/mg glomerulus, p<0.01). Consequently, a significant decrease of the heparan sulphate/4-hydroxyproline ratio (D: 0.21 (0.14–1.16) vs C: 0.39 (0.30–0.47), p<0.05) was found. In summary, we demonstrate that in streptozotocin-diabetic rats glomerular hyperfiltration and a progressive, selective proteinuria are associated with a relative decrease of glomerular basement membrane heparan sulphate. Functionally, a diminished heparan sulphate-associated charge density within the glomerular basement membrane might explain the selective proteinuria in the diabetic rats.Abbreviations BW Body weight - ERPF effective renal plasma flow - GAG glycosaminoglycan - GBM glomerular basement membrane - GFR glomerular filtration rate - HS heparan sulphate - HSPG heparan sulphate proteoglycan - IDDM insulin-dependent diabetes mellitus - STZ streptozotocin     

伊贝沙坦对大鼠糖尿病模型肾脏肥大和肾小球毛细血管基底膜厚度的影响

目的 观察伊贝沙坦对大鼠糖尿病模型肾脏肥大和肾小球毛细血管基底膜厚度的影响。方法 将SD大鼠分为糖尿病肾病组(A组)、伊贝沙坦治疗组(B组)、健康对照组(C组),A和B组大鼠制成糖尿病模型,B组予以50mg／kg伊贝沙坦灌胃。观察第4、8、12周大鼠的血糖、体重、尿白蛋白、24h尿蛋白的改变及第12周时的肌酐清除率(Ccr)、肾重、肾脏肥大指数、肾组织总蛋白含量、肾小球面积和体积、肾小球毛细血管基底膜(GBM)厚度的改变。通过免疫组化观察肾结缔组织生长因子(CTGF)和转化生长因子(TGF)-βl的表达。结果 A组和B组大鼠血糖较C组明显升高且维持在一个较高水平(P＜0．01)。A组大鼠的体重较C组明显下降,B组有所增加(P＜0．05)。随时间的推移(第4、8、12周),A组大鼠尿蛋白、尿白蛋白逐渐增加,B组明显减少(P＜0．01)。A组大鼠Ccr较C组显著升高(P＜0．01),B组Ccr明显下降(P＜0．05)。至第12周时,A组大鼠肾脏重量、肾脏肥大指数、肾组织总蛋白含量、肾小球面积和体积均较C组明显增加(P＜0．01),B组均较A组降低(P＜0．01,P＜0．05)。免疫组化半定量分析显示,A组大鼠CTGF与TGF-βl的表达均高于C组(P＜0．01),B组明显低于A组(P＜0．01,P＜0．05)。A组大鼠GBM较C组明显增厚(P＜0．01),B组较A组明显变薄(P＜0．01）。肾小球CTGF、TGF—βl的表达与肾脏体积呈正相关(r＝0．83,r＝0．83;P＜0．05)。结论 早期应用伊贝沙坦可抑制糖尿病大鼠早期肾脏肥大和CTGF表达等。     

Effect of octreotide and insulin on manifest renal and glomerular hypertrophy and urinary albumin excretion in long-term experimental diabetes in rats

Summary Treatment of diabetic rats with octreotide can inhibit early diabetic renal hypertrophy. Octreotide administration for 6 months from the day of diabetes induction inhibits renal hypertrophy and diminishes increase in urinary albumin excretion. To investigate the effect of octreotide on manifest diabetic renal changes, octreotide treatment was given for 3 weeks after an untreated diabetic period of 3 or 6 months. In addition, following 6 months of diabetes, a group of diabetic rats was treated with insulin for 3 weeks. Renal and glomerular hypertrophy, and increased urinary albumin excretion were observed in diabetic rats compared to non-diabetic control rats from 3 months and throughout the study period. Octreotide treatment did not affect body weight, food intake, blood glucose or serum fructosamine levels. We observed no effect of octreotide treatment on renal and glomerular hypertrophy or urinary albumin excretion compared to placebotreated diabetic rats. Insulin treatment for 3 weeks after 6 months of untreated diabetes normalized blood glucose and serum fructosamine levels, and furthermore renal hypertrophy was significantly diminished compared to the placebo-treated diabetic rats. However, insulin treatment had no effect on glomerular hypertrophy or urinary albumin excretion. In conclusion, octreotide treatment for 3 weeks following an untreated diabetic period of 3 or 6 months is unable to reduce the increased renal and glomerular volume or urinary albumin excretion. However, insulin treatment for 3 weeks with induction of euglycaemia diminishes the renal hypertrophy but has no effect on glomerular volume or urinary albumin excretion.Abbreviations UAE Urinary albumin excretion - IGF-I insulin-like growth factor I - IGFBP insulin-like growth factor binding protein - STZ streptozotocin - TGV total glomerular volume - BW body weight - GH growth hormone - RPF renal plasma flow     

Modification of the glomerular basement membrane in sucrose-fed and streptozotocin-diabetic rats

Summary Rats were fed on diets containing either sucrose or starch as the carbohydrate component (55%) for eight months. Diabetes was induced in animals of both groups by injecting streptozotocin (50 mg/kg body weight). Diabetic rats failed to gain weight, had enlarged kidneys, polyuria and elevated blood glucose levels. Starch and sucrose fed rats gained weight normally and had normal blood glucose levels. Sucrose fed rats had enlarged kidneys. Regional thickening of the glomerular basement membrane was present in sucrose-fed and diabetic rats but not in starch-fed controls. Glomerular basement membrane isolated from pooled kidney cortices from rats in the different experimental groups were analysed for amino acid, disaccharide and hexosamine content. Hydroxylysine (9 to 20%), hydroxyproline (21 to 24%), disaccharide (27%) and hexosamine (26%) were increased in membranes insolated from the three experimental groups, compared with starch-fed non-diabetic controls. An increase in low molecular weight components of the glomerular basement membrane of sucrose-fed and diabetic rats was observed using electrophoresis in sodium dodecyl sulphate. Significantly higher (p<0.001) glucosyltransferase activity was present in kidney supernatants prepared from sucrose-fed (1050±60 nmol/2 h/kidney) compared to starch-fed rats (510±40 nmol/2 h/kidney). Sucrose feeding induces changes similar to those found in diabetes and the induction of diabetes made little difference over the feeding of sucrose alone.     

洛沙坦对大鼠糖尿病模型肾脏转化生长因子βⅠ型、Ⅱ型受体表达的影响

目的　观察洛沙坦对大鼠糖尿病模型肾脏转化生长因子 βⅠ型受体 (TGFβRⅠ )、Ⅱ型受体 (TGFβRⅡ )表达的影响。 方法　 30只大鼠按体重随机分为 3组 ,每组 10只。A组 :健康对照组 ;B组 :糖尿病模型组 ,尾静脉注射链脲佐菌素 5 0mg/kg体重制成糖尿病模型 ;(3)C组 :洛沙坦治疗组 ,按B组方法建立大鼠糖尿病模型后第 2天给予洛沙坦 10mg·kg体重 -1·d-1灌胃。 8周后半定量逆转录 聚合酶链反应检测 3组肾皮质TGFβRⅠ、TGFβRⅡ和纤维连接蛋白 (FN)mRNA的表达。免疫组化测 3组肾皮质TGFβRⅠ、TGFβRⅡ和FN蛋白的表达。生化法测血糖、尿素氮和肌酐水平。放射免疫法测血胰岛素和血管紧张素Ⅱ。磺基水杨酸法测 2 4h尿蛋白。结果　B组大鼠平均肾小球体积、肾重 /体重增加 ,2 4h尿蛋白、血尿素氮和肌酐水平上升 (P <0 0 5 ) ;肾皮质TGFβRⅠ、TGFβRⅡ、FNmRNA和蛋白表达显著增加 (P <0 0 5 )。C组大鼠平均肾小球体积、肾重 /体重减少 ,2 4h尿蛋白、血尿素氮和肌酐水平下降 (P <0 0 5 ) ;肾皮质TGFβRⅠ、TGFβRⅡ、FNmRNA和蛋白表达显著降低 (P <0 0 5 )。 结论　洛沙坦下调大鼠糖尿病模型肾脏TGFβRⅠ、TGFβRⅡ的表达 ,抑制肾脏细胞肥大 ,减少细胞外基质成分的合成。     

低分子量肝素对免疫复合物型肾炎大鼠纤溶酶原激活物抑制剂-1的影响

目的　观察低分子肝素 (LMWH)治疗免疫复合物型肾炎大鼠蛋白尿的效果及其对肾组织纤溶酶原激活物抑制剂 - 1 (PAI- 1 )的作用。方法　将 2 0只大鼠平均分为正常组、对照组、模型组及 L MWH治疗组。模型组及 LMWH治疗组大鼠以阳离子化小牛血清白蛋白 (C- BSA)诱导成为免疫复合物型肾炎 ,LMWH治疗组以 1 2 5u日 1次皮下注射 ,共治疗 8w。结果　 L MWH治疗组尿蛋白下降 ,肾组织中 PAI- 1、纤维粘连蛋白(FN)、层粘连蛋白 (LN)较模型组明显下降 (P<0 .0 5) ,肾小球系膜基质增生有显著改变 ,但上述各项指标均未达到正常组及对照组水平 (P>0 .0 5) ;各组凝血酶原时间 (PT) ,部分凝血活酶时间 (APTT)比较差别无显著意义。结论　 L MWH可以降低免疫复合物型肾炎大鼠蛋白尿 ,降低肾组织中PAI的表达 ,通过干扰 PAI- 1减轻肾小球系膜基质增生 ,而且出血危险性小 ,便于长期应用。     

低分子肝素对子痫前期样大鼠肝脏保护作用研究

目的研究低分子肝素（Low Molecular Weight Heparin,LMWH）对子痫前期样大鼠肝脏组织的保护作用．并从抗细胞凋亡角度探讨其可能的作用机制。方法取10只正常非孕鼠为正常非孕组,另将30只孕鼠随机分为正常孕组、子痫前期组（preeclampsiagroup,PE组）及LMWH治疗组。PE组及LMWH治疗组孕鼠均于妊娠第13天开始给予左旋硝基精氨酸甲酯（L—NAME）200mg·kg-1·d-1皮下注射,共5d．建立子痫前期样孕鼠模型。PE组于妊娠第15～20天给予生理盐水0．5ml皮下注射,LMWH治疗组于妊娠第15～20天给予LMWH40μl·kg-1·d-1皮下注射。检测各组血压、尿蛋白及ALT、AST,对LMWH疗效进行评价;采用TUNEL法检测肝脏细胞凋亡率,荧光定量PCR及WesternBlot法检测分别检测肝脏组织中caspase-3、Bcl-2及BaxmRNA和蛋白表达。结果与PE组相比,LMWH组血压及尿蛋白显著降低（P〈0．05）,转氨酶J蝴及AST显著降低（P〈0．05）;LMWH组肝脏细胞凋亡率、Caspase-3mRNA及活化Caspase-3蛋白表达均显著低于PE组（P〈0．05）,Bcl-2mRNA及蛋白表达显著升高,而BaxmRNA及蛋白则显著降低（P〈0．05）。结论低分子肝素可以有效改善子痫前期样大鼠肝功能,减少肝脏细胞凋亡。对其肝脏具有保护作用,这一作用可能通过调节Bcl-2／Bax平衡抑制细胞凋亡。