口服低剂量混合稀土“常乐”对糖尿病大鼠肾脏损伤的修复作用

目的：通过探讨口服低剂量混合稀土“常乐”对糖尿病大鼠肾脏形态结构的影响,阐明其对糖尿病大鼠肾脏损伤的修复作用。方法：Wistar雄性大鼠制备糖尿病大鼠模型,造模成功的大鼠分为糖尿病模型组（10只）和“常乐”给药组（10只）,另取10只正常大鼠作为对照组,3组大鼠分别每日给予生理盐水、“常乐”（0.2 mg?kg-1）灌胃1个月,处死取肾脏,采用形态计量技术检测各组大鼠肾脏的质量、体质量、肾质量与体质量比、肾皮质厚度、肾小球体密度、肾小球总体积、近（远）端小管总体积、近（远）端小管上皮细胞高度、近（远）端小管管腔直径及肾脏的形态学。结果：与对照组和“常乐”给药组比较,糖尿病模型组肾脏质量明显增加（P<0.01）、体质量明显减轻（P<0.01）、肾质量与体质量比明显升高（P<0.01）、肾小球总体积明显增大（P<0.01）、近（远）端小管总体积明显增大（P<0.01）、近端小管上皮细胞高度明显增高（P<0.01）、近（远）端小管管腔直径明显增大（P<0.01）、肾皮质厚度和肾小球体积及远端小管上皮细胞高度无变化（P>0.05）;与对照组比较,“常乐”给药组大鼠肾脏的质量、肾皮质厚度、肾小球体密度、肾小球总体积、近端小管总体积、近（远）端小管上皮细胞高度、近（远）端小管管腔直径均无明显变化（P>0.05）,体质量明显减轻（P<0.01）,肾质量与体质量比明显增加（P<0.01）,远端小管总体积明显增加（P<0.01）。HE染色,对照组大鼠肾脏未见异常;糖尿病模型组大鼠肾脏肿胀,见大量炎细胞浸润。PAS染色,糖尿病模型组大鼠大部分近端小管上皮细胞明显肿胀,含PAS阳性物质增多,有少数近端小管可见上皮细胞脱落和管腔扩张,远端小管部分扩张,但上皮细胞无明显改变;“常乐”给药组大鼠近端小管上皮细胞略微肿胀,少量PAS阳性物质,无近端小管上皮细胞脱落和管腔扩张及远端小管扩张。结论：口服低剂量混合稀土“常乐”对糖尿病大鼠肾脏损伤具有修复作用。     

经口给予钒酸盐对糖尿病大鼠肾脏影响的形态计量研究

本实验用形态计量技术研究经口慢性给予钒酸钠对实验性糖尿病大鼠肾脏结构的影响。研究结果表明,投给钒酸钠可使糖尿病动物肾脏重量明显减轻,肾小球总体积显著减小。钒处理使近端小管和远端小管总体积恢复正常,并使已扩张的肾小管缩小。钒处理可使糖尿病大鼠已损伤的肾脏结构基本恢复正常。     

经口给予钒酸盐对糖尿病大鼠肾脏影响的形态计量研究

本实验用形态计量技术研究经口慢性给予钒酸钠对实验性糖尿病大鼠肾脏结构的影响。研究结果表明，投给钒酸钠可使糖尿病动物肾脏重量明显减轻，肾小球总体积显著减小。钒处理使近端小管和远端小管总体积恢复正常，并把已扩张的肾小管缩小。钒处理可使糖尿病大鼠已损伤的肾脏结构基本恢复正常。     

大鼠早期糖尿病肾小球及肾小管的动态病理变化

目的 :探讨大鼠早期糖尿病肾小球基膜和肾小管基膜的动态变化。方法 :采用PAS染色和计算机图像分析检测大鼠早期糖尿病肾小球直径、截面积以及肾小球基膜厚度和肾小管基膜厚度的动态变化。同时观察实验动物血糖和肾脏肥大指数的变化。结果 :糖尿病大鼠 1～ 4周肾小球系膜细胞外基质 (ECM)增加 ,PAS阳性物质逐渐增多 ,肾小球基膜和肾小管基膜的厚度明显较正常对照增厚 (P <0 .0 1) ,且随病程延长呈进行性增厚。结论 :大鼠早期糖尿病已出现肾小球形态变化并有ECM增加 ,肾小球基膜和肾小管基膜增厚 ,且随病程延长呈进行性加重。     

血糖波动与持续性高血糖对糖尿病大鼠肾脏病理改变及IV型胶原表达的影响

目的: 观察血糖波动与持续性高血糖对糖尿病大鼠肾脏病理改变及 IV型胶原(Col IV)表达的影响。方法: 将60只SD雄性大鼠随机分为正常组和模型组,正常组大鼠喂以普通饲料,模型组大鼠高糖高脂饲料喂养6周后予以小剂量链脲佐菌素(STZ,30mg/kg)皮下注射制造糖尿病大鼠模型。再将糖尿病组大鼠随机分为持续性高血糖组和血糖波动组,其中血糖波动组给予每日两次皮下注射胰岛素人为诱导血糖波动。3个月后将大鼠剖腹取出肾,行HE染色、PAS染色、Col IV免疫组织化学及Western印迹检测。结果: 与正常组大鼠比较,模型组大鼠肾小球体积增大、毛细血管内皮细胞基底膜增厚、系膜基质增多、肾小球球囊腔扩张,肾小管体积增大、肾小管管腔扩张、上皮细胞基底膜增厚,肾小球通透性增强,肾脏病理形态改变明显;肾肥大指数增加、肾小球硬化指数增加、Col IV表达量明显增加(P<0.01)。与持续性高血糖组比较,血糖波动组大鼠上述指标变化更为明显(P<0.05)。结论: 糖尿病大鼠出现了肾小球基底膜增厚、系膜基质增多等病理形态的改变,血糖波动组肾小球硬化更明显, Col IV的增多可能与糖尿病肾病的严重程度有关。     

常染色体显性多囊肾病Han:SPRD大鼠肾脏病理观察及其意义

目的:观察常染色体显性多囊肾病(autosomal dominant polycystic kidney disease, ADPKD)的Han:SPRD大鼠模型的肾脏病理变化,为揭示ADPKD发病机制提供证据与线索.方法:选取雄性2周龄Han:SPRD纯合大鼠(cy/cy)和3个月龄杂合大鼠(cy/ ),取其肾组织进行H-E染色、PAS染色、Masson染色以及透射电镜观察.结果:光镜下发现Han:SPRD大鼠肾脏体积增大;囊肿衬里上皮细胞增殖显著;小管基膜增厚,可见灶性小管萎缩和较多蛋白管型;肾小球数目减少、体积缩小,渐趋废弃,呈明显缺血样改变,血管壁增厚.透射电镜可见肾小球毛细血管腔阻塞,基底膜薄厚不均,部分断裂;小管上皮细胞胞质脱落,微绒毛紊乱、部分缺如;细胞外间质成分稀少;囊肿衬里上皮细胞内可见大量线粒体,高尔基体、核糖体丰富.结论:Han:SPRD大鼠肾脏组织学和超微结构的改变可解释多囊肾病的部分临床表现;并观察到Han:SPRD大鼠肾小管上皮细胞微绒毛异常,为揭示疾病的发病机制提供了线索.     

STZ诱导糖尿病肾病大鼠模型的建立

目的建立糖尿病大鼠动物模型,探讨其肾脏损害规律。方法用STZ65mg/kg一次性腹腔内注射方式制作糖尿病大鼠模型,设立空白对照组,饲养14周,期间观察大鼠血糖、尿糖及一般情况变化,实验结束时测定血肌酐、尿素氮、尿蛋白、尿白蛋白排泄率,取肾作病理及超微病理检查。结果模型组大鼠出现血肌酐、尿素氮、尿蛋白、尿白蛋白明显升高,出现肾脏肥大,病理显示明显的肾小球、肾小管病变。结论STZ诱导糖尿病大鼠肾脏表现肾小球及小管间质损害,可以用作糖尿病肾病研究的动物模型。     

牛磺酸减轻糖尿病大鼠肾脏功能和结构损害

目的：研究牛磺酸对糖尿病大鼠肾脏功能和结构损害的减轻效果。方法：糖尿病大鼠用牛磺酸（１％ 饮水）处理１４ 周后,检查肾脏功能和结构的损害程度。结果：与对照组大鼠相比,糖尿病大鼠血糖、血清肌酐（Ｓｃｒ）、尿素氮（ＢＵＮ）水平和尿白蛋白排泄量明显升高。牛磺酸处理未使血糖水平明显降低,但Ｓｃｒ、ＢＵＮ 和尿白蛋白排泄量明显下降。给予牛磺酸后使糖尿病大鼠已升高的肾小球体积／体重比明显降低。糖尿病大鼠肾小球基底膜呈节段性增厚,上皮足突部分融合和滤过膜间隙增大。牛磺酸处理后这些超微结构改变明显改善。结论：牛磺酸对糖尿病大鼠肾脏功能和结构损害有明显减轻作用     

转化生长因子β1在糖尿病大鼠肾脏表达中的研究

目的探讨链脲佐菌素（streptozotocin,STZ）诱导的糖尿病大鼠转化生长因子β1（Transforming growth factor-β1,TGF-β1）的表达情况。方法实验采用成年雄性Sprague-Dawle大鼠20只,随机分为两组各10只,糖尿病组尾静脉注射STZ制成糖尿病模型,对照组尾静脉注射枸橼酸钠缓冲液。两组大鼠4周后处死,取肾脏组织行苏木精伊红染色法观察糖尿病肾脏组织的形态变化,同时行免疫组织化学SABC半定量检测TGF-β1蛋白的表达水平。结果糖尿病组肾脏组织光镜下出现肾小球的毛细血管球肥大,肾小囊腔呈裂隙状,基底膜轻度增厚,系膜增生,肾小管上皮细胞显示空泡和颗粒变性。TGF-β1蛋白在糖尿病大鼠肾脏上皮细胞和肾小球系膜细胞表达显著增高（P〈0.01）。结论实验动物的高血糖状态会损害肾脏组织,高血糖可能通过活化大鼠肾脏组织内TGF-β1,从而促进肾间质结缔组织增生和纤维化,从而导致肾小球硬化而引起糖尿病肾病。     

螺内酯对糖尿病大鼠肾小管间质的保护作用

目的:观察螺内酯对糖尿病大鼠肾小管间质的保护作用并探讨其机制。方法:雄性SD大鼠,随机分为健康对照组、糖尿病组和螺内酯治疗组。8周后检测各组大鼠血压、24 h尿蛋白定量、血肌酐、血钾、血糖、内生肌酐清除率;留取肾组织作PAS染色行病理检查;采用免疫组织化学技术检测近端肾小管上皮细胞醛固酮受体(MR)、检测肾小管-间质中基质金属蛋白酶-2(MMP-2)及α-平滑肌肌动蛋白(-αSMA)表达,并做半定量分析。结果:各组大鼠肾脏近端小管上皮细胞胞质内均有MR表达,与健康对照组相比,糖尿病组近端小管MR表达上调,螺内酯对MR的表达无影响;糖尿病组大鼠肾小管间质MMP-2、-αSMA表达均显著高于对照组(P<0.01),螺内酯治疗8周后,肾组织MMP-2及-αSMA明显下调(P<0.01),肾功能指标及组织病理学损害得以改善,而螺内酯对大鼠的血压、血钾没有影响(P>0.05)。肾组织内-αSMA与MMP-2的表达具有明显的正相关关系(r=0.920,P<0.01)。结论:大鼠近端小管上皮细胞存在MR的表达,糖尿病肾内MR表达增加可能是醛固酮促肾纤维化的部分原因;螺内酯对糖尿病大鼠肾小管间质病变具有保护作用,其机制至少部分与抑制肾小管上皮-肌成纤维细胞转分化,下调肾小管间质中MMP-2、-αSMA表达有关。     

1型糖尿病大鼠肾小管间质纤维化的病理改变

目的探讨不同病程1型糖尿病大鼠模型肾小管问质的病理变化。方法腹腔注射链尿佐菌素（STZ,65mg／kg）建立SD大鼠1型糖尿病模型,注药后7d造模成功后分别于4周、12周和24周Masson染色观察血管周围胶原面积（PVCA）、肾小管间质病变评分（TILS）,用免疫组织化学法对肾脏胶原蛋白（collagenⅠ、collagenⅢ）在肾脏的分布及表达进行半定量分析,肾脏光镜与电镜观察,并与同龄正常大鼠进行比较。结果与正常对照组比较,糖尿病组肾脏纤维化指标PVCA、TILS、collagenⅠ、collagenⅢ的表达均明显增高（P〈0．05）。电镜发现糖尿病组肾小球毛细血管基底膜弥漫性增厚,近曲小管上皮细胞空泡化。结论早期糖尿病大鼠模型已出现肾小管间质纤维化改变,损伤的肾小管问质有助于早期判断糖尿病肾病肾脏损伤程度。     

Caspase-3在缺氧和内毒素致肾小管损伤的肾组织表达

目的 为了建立缺氧和内毒素致肾小管损伤模型,观察Caspase-3在肾组织的表达,以探讨其肾小管的损伤机制.方法 以SD大鼠为实验动物,予麻醉及机械通气,同时予阴茎静脉注射伤寒杆菌脂多糖,吸入氧浓度从21%降至5%的氧,通气至180rain结束.取肾组织作HE染色病理切片检查及用Caspase-3免疫组化S-P法染色观察模型肾组织的病理改变及肾组织中Caspase-3的表达.结果 (1)病理组织学所见:大部分肾小球充血,内皮及系膜细胞轻度肿胀,肾近曲小管上皮明显肿胀,呈浊样改变;大部分远曲小管镜下未见明显改变,部分上皮细胞肿胀,浊样变性在;整个肾间质呈充血现象.无炎性细胞浸润,(2)免疫组化结果:Caspase-3染色位于胞浆,大部分远曲小管上皮呈Caspase-3阳性反应,以外髓远曲小管为明显;近曲小管偶见Caspase-3阳性细胞,肾小球Caspase-3染色阴性.结论 (1)缺氧及内毒素可致肾小管损伤,且以近曲小管为著,远曲小管及内髓部损伤相对较轻,(2)Caspase-3在远曲小管明显表达,提示在缺氧及内毒素致肾小管损伤中,同时存在细胞变性坏死及细胞凋亡,近曲小管以细胞变性坏死为著,而远曲小管细胞凋亡明显.

Abstract：

Objectives To observe the expression of caspase-3 in the kidney of a rat model of renal tubular damage induced by endotoxin and hypoxia and explore the mechanism of renal tubular damage. Methods Ten rats were anesthetized with artificial ventilation and received 2 mg/kg lipopolysaccharide (LPS) injection through the penile vein. The FiO_2 was reduced 90 min later from 21% to 5%, and the ventilation was withdrawn after another 90 min. Immediately after ventilation withdrawal, the kidney of the rats were obtained for immunocytochemistry and HE staining. Results HE staining showed obvious hyperemia in most of the glomeruli, mild swelling of the endothelial and mesangial cells, severe swelling and turbidity in the proximal tubular epithelial cells without obvious changes in most of the distal proximal tubules. A small portion of the interstitial epithelial cells showed swelling and turbidity, and the entire renal interstitium appeared hyperemic but without inflammatory cell infiltration. Immunocytochemistry detected the presence of caspase-3 in the cytoplasm, and most of the distal renal tubule cells were positive for caspase-3, while only occasional cells showed caspase-3 positivity in the proximal tubular epithelial cells. Most of the proximal tubular epithelial and glomerulus cells were negative for caspase-3. Conclusions Endotoxin and hyoxia can induce renal damage, particularly in the proximal renal tubule cells, and the distal tubular epithelial cells sustain relatively light damage. Caspase-3 is strongly expressed in the distal renal tubular cells, suggesting that in renal tubular damage induced by endotoxin and hypoxia, cell degeneration, necrosis and apoptosis coexist in the tubular epithelial cells; degeneration and necrosis occur primarily in the proximal tubular epithelial cells, while apoptosis is obvious in the distal renal cells.     

EARLY CHANGES OF KIDNEY MORPHOLOGY AND FUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

In order to study the nephropathy associated with experimental streptozotocin diabetes, serial functional and ultrastructural studies were done in insulin-treated (Group T), untreated (Group D) diabetic Wistar rats and normal controls on d 3, d 8, d 14 and d 28 of diabetes. The ratio of kidney weight to the body weight (KW/BW) and mean glomerular diameter (MGD) in diabetes rats at varying durations were increased as compared with those in control animals, but an increase of KW/BW and MGD in Group D was more marked than in Group T. The creatinine clearance (Ccr) and total urinary protein excretion rate (TUPER) were increased in Group D end T, but the increase in TUPER appeared later in Group T than in Group D. Enlargement of epithelial cells, disappearance of folds on their surface and widening of foot processes were observed after 3 d of diabetes. After 14 d of diabetes, increased basement membrane-like material in the mesangium was found. Morphologically an increase in glomerular size, expanded foot processes with ball-like terminal expansions, thickened basement membrane were observed.     

2型糖尿病患者肾小管功能的改变

目的　观察 2型糖尿病患者肾小管功能的改变。方法　对 45例 2型糖尿病患者的尿酸化功能、视黄醇结合蛋白 (RBP)及渗透压进行了检测。结果　 12型糖尿病患者尿中可滴定酸 (TA)、铵离子 (NH+ 4)、净酸排泄量(NAC)及尿渗透压均显著低于正常对照 (P<0 .0 5 ,P<0 .0 1)。尿 RBP排泄量则明显高于正常对照 (P<0 .0 1)。2这些肾小管功能异常在肾小球滤过功能尚未明显受损时即已出现 ,并随肾小球病变加重而更趋显著。结论　 2型糖尿病患者肾小管损害亦相当常见 ,它在糖尿病肾病 (DN)的发生发展中起着与肾小球病变同样重要的作用     

Tubuloglomerular Feedback Response in the Contralateral Kidney after 24-hour Unilateral Ureteral Obstruction

Reduction of the functioning renal mass by unilateral nephrectomy or unilateral ureteral occlusion (UUO) leads to increased function of the remaining nephrons, an important factor being the glomerular filtration rate (GFR). GFR can be modified via the tubuloglomerular feedback control (TGF), which senses the distal delivery of fluid and alters the tonus of the glomerular arterioles. The aim of the present study was to investigate the TGF sensitivity in the intact left kidney of rats after 24 hours of right ureteral occlusion. Using a micropuncture technique, proximal tubular stop-flow pressure (P_sf), as a relative index of glomerular capillary pressure, was measured upstream to the block, while late proximal segments were perfused with Ringer solution (rates 0–40 nl/min). The maximal drop in P_sf and the tubular flow rate at which 50% of this response was achieved, the turning point (TP), were determined. Considerable decrease in the sensitivity of the TGF system in the contralateral kidney during UUO was indicated by a significantly higher TP as compared with control rats (sham operation), viz. 29 v. 19 nl/min. Maximal P_sf drop after UUO was significantly less than in the controls (6 v. 12 mm Hg). Reduced TGF sensitivity in the contralateral kidney after protracted UUO is a prerequisite for that kidney's increased excretion of salt and water to compensate for the loss of functioning renal mass.     

1型糖尿病对血脂代谢及肾和心脏组织结构的影响

目的探讨1型糖尿病对血脂代谢及肾和心脏组织结构的影响。方法随机选取新西兰大白兔36只，分为糖尿病组（DM，20只）和对照组（NC，16只），两次四氧嘧啶（ALX，80mg/kg）耳缘静脉注射复制1型糖尿病模型，期间进行血糖控制。饲养4周，观察兔一般情况，4周末采血检测血脂变化，包括TG、TC、LDL- C、HDL- C水平、载脂蛋白（Apo）A1、ApoB100、ApoE，处死兔后膀胱穿刺抽取尿液检测尿常规和尿蛋白定量，分离心脏和肾脏进行病理组织检查。结果实验造模成功率为55%，死亡率为40%。DM组TC、HDL- C、LDL- C水平显著高于NC组（P＜0.01），其中TC、TG、LDL- C水平较NC组分别升高97%,48%,130%。DM组TC/HDL- C, LDL- C/HDL- C水平高于NC组（P＜0.01），但TG/HDL- C水平低于NC组；两组ApoB100、ApoA1/ApoB100、ApoE差异无统计学意义（均P＞0.05）。DM组尿蛋白定量较NC组升高。DM组心肌病理检查出现轻度-中-重度不同程度的心内膜下脂肪变性和沉积，肾脏病理检查提示肾小球血管袢分叶数量增加，基底膜及系膜基质增生，肾小球体积缩小，部分出现脂肪变替代，肾小管出现不同程度范围变性甚至坏死，腔内可见钙盐沉积。结论1型糖尿病可导致脂质代谢紊乱，引起心脏和肾脏病变，需行积极降脂治疗。     

Associations between urinary kidney injury biomarkers and cardiovascular mortality risk in elderly men with diabetes

Aim: Three urinary biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C, have been suggested as clinically relevant highly specific biomarkers of acute kidney tubular damage. Yet, the utility of these biomarkers in the prognostication of diabetic nephropathy has been less studied. Therefore, we aimed to investigate the longitudinal association between these urinary biomarkers and cardiovascular mortality in patients with diabetes.

Methods: The study sample consisted of participants with diabetes in the community-based Uppsala Longitudinal Study of Adult Men (n?=?91; mean age 77.8 years). During follow-up (median 8.3 years, interval 0.7–13.4 years), 33 participants died of cardiovascular causes.

Results: In a multivariable Cox regression model adjusting for age, glomerular filtration rate, and urinary albumin/creatinine ratio, higher urinary KIM-1/creatinine was associated with an increased risk for cardiovascular mortality (HR per SD increase 1.51, 95% confidence intervals 1.03–2.24, P?=?0.03). Neither urinary NGAL/creatinine nor urinary cystatin C/creatinine were independently associated with an increased cardiovascular mortality risk.

Conclusion: In elderly men with diabetes, higher urinary KIM-1/creatinine was associated with an increased long-term risk of cardiovascular mortality independently of established markers of diabetic nephropathy. Our data provide support for kidney tubular damage as an important aspect of diabetic nephropathy that merits further investigation.     

厄贝沙坦对STZ诱导的糖尿病大鼠肾脏CTGF、p27kip1表达的影响

目的:观察厄贝沙坦(Irb)对大鼠糖尿病模型肾脏结缔组织生长因子(CTGF)、p27k ip1表达的影响。方法:将SD大鼠分为健康对照组(C组)、糖尿病肾病组(DN组)和糖尿病肾病Irb治疗组(DNI组),DN组和DNI组大鼠制成糖尿病模型,DNI组予以50 mg.kg-1伊贝沙坦灌胃。各组大鼠再分为4个亚组,分别于成模后1、2、4、8周时处死,观察各组大鼠的血糖、体重、24 h尿白蛋白、内生肌酐清除率(Ccr)、肾重、肾脏肥大指数、肾小球面积(AG)和体积(VG)、肾小管面积(AT)、肾小球基底膜(GBM)厚度、肾小管基底膜(TBM)厚度的改变,通过免疫组化观察肾CTGF和p27k ip1的表达。结果:DN组和DNI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)。C组体重增长迅速,DN组和DNI组大鼠体重增长缓慢(P<0.01)。DN组大鼠的24 h尿白蛋白、Ccr、肾重、肾脏肥大指数、AT和VG在糖尿病早期即呈时间依赖性增加(P<0.01或P<0.05)。免疫组化半定量分析显示,各期DN组大鼠肾小球和肾小管的CTGF、p27k ip1表达均高于C组(P<0.01或P<0.05)。8周时DN组大鼠GBM和TBM均较C组明显增厚(P<0.01),而Irb可显著抑制上述参数的增加。CTGF与p27k ip1的表达、24 h尿白蛋白、AT、AG、VG呈显著正相关关系(P<0.05)。结论:早期应用Irb可抑制糖尿病大鼠早期肾脏肥大和CT-GF与p27k ip1的表达,此为早期使用该药预防DN肾脏肥大的发生提供了新的理论依据。     

α-硫辛酸对糖尿病肾病模型大鼠肾组织转化生长因子-β1和结缔组织生长因子表达的影响

目的:通过α-硫辛酸对糖尿病肾病模型大鼠肾组织转化生长因子-β1(transforming growth factor-β1,TGF-β1)、结缔组织生长因子(connective tissue growth factor,CTGF)表达的影响,研究其延缓肾脏纤维化的作用及机制,为临床防治糖尿病肾病提供实验依据。方法:将50只健康SD大鼠随机分为正常对照组,糖尿病模型组和α-硫辛酸低、中、高剂量组。采用链脲佐菌素(streptozocin,STZ)以60 mg/kg于左下腹腔一次性注射建立大鼠糖尿病模型。α-硫辛酸低、中、高剂量组分别按15、30、60 mg/(kg.d)灌胃12周。检测各组大鼠的血糖、肾重指数,制备肾脏石蜡切片,测定肾小球平均截面积(MGA)并计算肾小球平均体积(MGV)。用SureStep Plus型血糖仪于实验结束前检测空腹血糖;经HE染色,光镜下观察肾小球体积,肾小球基底膜变化,用免疫组化法检测肾组织TGF-β1、CTGF的表达。结果:与正常组相比,模型组大鼠血糖明显升高;与模型组相比,α-硫辛酸各剂量组大鼠血糖显著降低;糖尿病模型组大鼠肾重指数明显增加,光镜显示糖尿病模型组大鼠的肾小球体积明显增大,系膜区增宽,毛细血管管腔受压,肾小球基底膜增厚,肾组织TGF-β1、CTGF蛋白表达明显降低;糖尿病模型组MGA和MGV明显扩大,与其相比,α-硫辛酸各剂量组有不同程度的缩小。结论:α-硫辛酸通过抑制肾组织TGF-β1、CTGF的表达而发挥其抗纤维化的作用,从而延缓STZ糖尿病大鼠肾脏纤维化的发展。