4-苯基丁酸对糖尿病肾病大鼠的作用

目的 探讨化学分子伴侣4-苯基丁酸（4-PBA）对糖尿病肾病（DN）大鼠的治疗作用及其机制。 方法 54只大鼠随机分为正常对照组（NC）、糖尿病肾病组（DN）和4-PBA治疗组（4-PBA）,每组各18只。在治疗第4、8及12周末分别检测各组大鼠肾质量指数（KI）、24 h尿蛋白排泄率（UAER）、血肌酐（Scr）、尿素氮(BUN)、尿丙二醛（MDA）含量和超氧化物岐化酶（SOD）活性;观察肾脏病理改变;实时荧光定量PCR法检测各组大鼠肾组织p47phox mRNA的表达变化;Western印迹检测p47phox和硝基酪氨酸（NT）的蛋白表达变化。 结果 与NC组大鼠比较,在4、8和12周时,DN大鼠的KI显著增高（P < 0.05）,UAER（mg/24 h）也显著增高（4.92±0.70 比 0.26±0.07、 5.29±0.83 比0.28±0.08、5.54±0.81比0.29±0.04,均P < 0.05）。12周时病理显示DN大鼠肾小球系膜细胞增生,系膜基质积聚;而与DN组大鼠比较,4-PBA治疗组大鼠KI显著降低（P < 0.05）,UAER（mg/24 h）亦显著降低（4、8和12周分别为3.71±0.37、3.47±0.36和3.28±0.40,P < 0.05）,4-PBA能显著减轻肾脏的病理变化。在4、8和12周,与NC组大鼠比较,DN大鼠肾组织p47phox mRNA表达分别升高了154.72%、148.60%和91.95%（均P < 0.05）;p47phox蛋白表达分别升高了118.00%、140.10%和177.82%（均P < 0.05）;硝基酪氨酸蛋白表达分别升高了45.29%、59.13%和89.28%（均P < 0.05）;尿MDA含量分别增加了2.05倍、2.26倍和2.43倍;尿SOD活性分别下降了64.78%、71.29%和79.32%。与DN组比较,在8和12周时,4-PBA治疗组DN大鼠肾组织p47phox mRNA和蛋白表达均显著减少（均P < 0.05）;硝基酪氨酸蛋白表达显著减少（P < 0.05）,且与NC组差异已无统计学意义。另外,在4~12周,4-PBA治疗可显著减少DN大鼠尿中MDA含量,增加尿SOD活性（均P < 0.05）。 结论 4-PBA能显著抑制糖尿病大鼠肾脏病理变化,其机制可能与抑制肾组织氧化应激有关。     

Quercetin ameliorates diabetic nephropathy by reducing the expressions of transforming growth factor-β1 and connective tissue growth factor in streptozotocin-induced diabetic rats

Diabetic nephropathy (DN) is one of the main causes of end-stage renal disease. Many studies have indicated that transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were involved in the pathophysiological mechanisms of DN. In addition, quercetin has been suggested to attenuate DN. In this study, we aim to examine whether quercetin ameliorates renal function through an effect on the expressions of TGF-β1 and CTGF in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intraperitoneal injection of STZ. The diabetic rats were then randomized to diabetic group and quercetin therapy group. At the end of the 12th week, blood glucose, body weight, kidney weight/body weight, urine albumin excretion (UAE), serum creatinine (sCr), blood urea nitrogen (BUN), and creatinine clearance (Ccr) were measured. The expressions of TGF-β1 and CTGF in the kidneys were determined using real-time PCR and Western blot method. Diabetic rats showed significant increases in blood glucose, kidney weight/body weight, UAE, sCr, BUN, and Ccr than control group. Treatment with quercetin improved these parameters except blood glucose. Compared with the control group, the expressions of TGF-β1 and CTGF were elevated in the diabetic group. The overexpressions of TGF-β1 and CTGF in the renal tissues of diabetic rats were attenuated by administration of quercetin. Our results suggest that quercetin improved renal function in rats with DN by inhibiting the overexpressions of TGF-β1 and CTGF in the kidney.     

红细胞生成素对糖尿病大鼠肾脏保护作用的机制

目的 观察红细胞生成素（EPO）对糖尿病大鼠的肾脏保护作用,并探讨其发挥肾脏保护作用的可能机制。 方法 将实验大鼠随机分为正常对照组（NC组）、糖尿病模型组（DM组）和EPO治疗组（DE组）。药物干预8周后,处死大鼠,检测尿白蛋白排泄率（UAER）、血清肌酐（Scr）、血细胞比容（Hct）。肾组织切片行HE、PAS染色,观察大鼠肾脏病理改变。化学比色法检测肾脏丙二醛（MDA）含量、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性及总抗氧化能力（T-AOC）。免疫荧光及Western印迹法检测大鼠肾脏EPO受体（EPOR）的表达。免疫组织化学及Western印迹法检测大鼠肾脏NADPH氧化酶亚基（p47phox）、转化生长因子β1（TGF-β1）、纤连蛋白（FN）的表达。 结果 EPO可以减轻糖尿病大鼠肾脏病理及功能改变。各组大鼠肾脏均表达EPOR,但表达水平比较差异无统计学意义（P ＞ 0.05）。与NC组相比,DM组大鼠p47phox、TGF-β1、FN蛋白表达增强（均P ＜ 0.01）;GSH-Px、SOD活性及T-AOC下降（均P ＜ 0.01）;MDA含量增加（P ＜ 0.01）。与DM组相比,DE组大鼠p47phox、TGF-β1、FN蛋白表达减弱（均P ＜ 0.05）;GSH-Px、SOD活性及T-AOC升高（均P ＜ 0.01）;MDA含量降低（P ＜ 0.01）。 结论 EPO可通过抑制糖尿病大鼠肾脏氧化应激,降低TGF-β1、FN表达,减轻糖尿病大鼠肾脏病理改变,发挥肾脏保护作用。     

法安明对糖尿病大鼠血清及肾组织中P-selectin的作用

目的：探讨P-selectin在糖尿病肾病发病中的作用以及低分子肝素法安明对肾脏保护作用的机制。方法：用链脲佐菌素（STZ60mg/kg体重）构建糖尿病大鼠模型后随机分为糖尿病组（DN组）和法安明治疗组（T组）,并设正常对照组（N组）。于应用法安明前、后第4、8、12周分别测定3组大鼠的体重、24h尿蛋白总量、24h尿白蛋白、Scr,12周测血脂、凝血功能;应用ELISA方法检测各组大鼠血P-selectin水平,用免疫组化方法检测肾组织P-selectin,用real-time PCR法测P-selectin mRNA表达;并观察各组大鼠肾脏组织病理学改变。结果：与N组比较,DN组大鼠肾重/体重指数以及24h尿白蛋白、蛋白定量、Scr均显著上升（P〈0.05）;肾组织P-selectin mRNA和蛋白表达增强（P〈0.01或P〈0.05）。与DN组比较,T组大鼠、肾重/体重指数下降（P〈0.05）、24h尿白蛋白、24h尿蛋白量和Scr均显著下降（P〈0.01）;P-selectin mRNA表达水平显著下降（P〈0.01）。结论：P-selectin可能参与了DN的发病过程,法安明可能通过影响P-selectin的表达从而对肾脏有保护作用。     

MG132可增强糖尿病大鼠肾脏抗氧化能力

目的 探讨蛋白酶体抑制剂MG132对糖尿病肾病（DN）大鼠的治疗作用及其机制。 方法 72只大鼠随机分为正常对照组（NC）、DN组和MG132治疗组（DN+MG132）,每组各24只。在治疗第4、8和12周末检测各组大鼠24 h尿蛋白排泄率（UPER）、24 h尿量和尿丙二醛（MDA）含量、肾组织26S蛋白酶体、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-PX）活性;实时荧光定量PCR法检测各组大鼠肾组织SOD、GSH-PX和p47phox mRNA的表达变化;Western印迹检测p47phox的蛋白表达变化。 结果 与NC组大鼠比较,在4、8和12周时,DN大鼠的UPER显著增高（均P < 0.05）;12周时病理显示DN组大鼠肾小球系膜显著增生和系膜基质积聚增多。与同期DN组大鼠比较,MG132治疗组大鼠的UPER显著降低（均P < 0.05）,肾小球系膜增生和基质积聚均减少。在4、8和12周,DN组大鼠肾组织26S蛋白酶体活性比NC组分别增高了2.14倍、2.66倍和3.68倍（均P < 0.05）。与DN组大鼠比较,MG132治疗组大鼠26S蛋白酶体活性显著下降（均P < 0.05）。与NC组大鼠相比,DN组大鼠肾组织p47phox mRNA表达分别升高了155%、149%和120%（均P < 0.05）;p47phox蛋白表达分别升高了139%、152%和186%（均P < 0.05）;尿MDA含量分别升高了1.95倍、2.04倍和2.62倍（均P < 0.05）;而DN大鼠肾组织SOD活性分别下降23.09%、33.59%和53.31%（均P < 0.05）;GSH-PX的活性分别下降28.57%、33.06%和48.76%（均P < 0.05）;SOD mRNA表达分别下降38.09%、61.44%和76.53%（均P < 0.05）,GSH-PX mRNA表达分别下降29.16%、37.26%和62.40%（均P < 0.05）。与DN组大鼠比较,MG132治疗组大鼠肾组织p47phox mRNA和蛋白表达以及尿MDA含量则显著下降（均P < 0.05）,而SOD和GSH-PX的活性和mRNA均显著升高（均P < 0.05）。 结论 MG132对DN大鼠肾脏有显著的保护作用,其机制可能与增强肾组织抗氧化能力有关。     

The Puerarin improves renal function in STZ-induced diabetic rats by attenuating eNOS expression

Abstract

Diabetic nephropathy (DN) is a serious complication and it leads to kidney failure. The endothelial nitric oxide synthases (eNOS) seems to be involved in the development and progression of DN. The Puerarin is a well-known Chinese traditional formula, which is widely used in clinical practice for the treatment of kidney disease. The present study was designed to investigate the renal protective effects of Puerarin on streptozotocin (STZ)-induced diabetic rats. Thirty Sprague–Dawley (SD) male rats were divided into three groups at random. The diabetic group and the Puerarin-treated group were intraperitoneally injected with STZ 65?mg/kg and the Puerarin-treated rats were intraperitoneally injected Puerarin 100?mg/kg/day for 4 weeks. The results showed the Puerarin could improve body weight, blood sugar, BUN and SCr levels, and reduce ultrastructural changes of kidney in diabetic rats. It also attenuated eNOS expression in glomerular endothelial cells and tubular cells of diabetic rats with Puerarin treatment (p?<?0.05). The Puerarin had significant renal-protective effects for the diabetic nephropathy, possibly through regulating eNOS expression, and it may be used as a potential therapeutic reagent.     

Effect of mycophenolate mofetil on CD26 expression in the kidneys of diabetic rats

Objective To investigate the expression of CD26 (dipeptidyl peptidase 4) in the kidney tissues of diabetic rats and the effects of mycophenolate mofetil (MMF) on the renal CD26 expression. Methods Wistar rats were randomly divided into three groups: normal control group (NC group, n=7), diabetic model group (DM group, n=7) and MMF-treated group (MMF group, n=7). Wistar rats were fed with high-sucrose-high-fat diet and injected with streptozotocin into abdominal cavity to induce diabetes. Sixteen weeks later, blood glucose (BG), blood urea nitrogen (BUN), serum creatinine (Scr), renal hypertrophy index (kidney weight/body weight) and 24 hour urinary protein (24Upro) were measured. The number of CD3+/CD4+ T cells in renal tissues were measured through flow cytometry. The expression of CD26 in kidney was examined by using Western blotting and immunohistochemistry. Results Compared with NC group, BG, BUN, Scr, kidney weight/body weight, 24Upro were significantly increased in DM group (P﹤0.05). Except BG and kidney weight/body weight, the above-mentioned parameters were lower in MMF group compared with that in DM group (P﹤0.05). Intrarenal CD3+/CD4+ T cells were significantly up-regulated in DM group compared with that in NC group (P﹤0.01). CD26 in renal tissue was mainly expressed in T lymphocytes of renal interstitium. CD26 expression in DM group was significantly higher than that in NC group, and also higher than that in MMF group (P﹤0.05). In DM group, CD26+ T lymphocytes infiltration of renal interstitium was positively correlated with 24Upro (r2=0.770, P﹤0.05). Conclusions CD26 is related with diabetic nephropathy. MMF maybe inhibit T lymphocytes infiltration to reduce the expression of CD26 in renal interstitium, thus protecting the kidney function.     

Effects of bone morphogenetic protein 2 signal pathway on renal artery calcification in progression of diabetic nephropathy

Objective To explore the effects of renal artery calcification on the progression of diabetic nephropathy (DN), the activation and its role of bone morphogenetic protein 2(BMP2) signal pathway in renal artery of rats. Methods Sixty male SD rats were randomly divided into control group(CON group), DN group and DN with vascular calcification group (DN+VDN group). Rats of group DN and DN+VDN were fed with high sugar and fat diet and injected with streptozocin (STZ) into abdominal cavity to induce diabetes. After diabetic models were successfully made, rats of group DN+VDN were treated by vitamin D3 plus nicotine. The rats were sacrificed at 8th, 12th and 16th week respectively and the levels of renal function, blood glucose and 24 h urinary protein (24-h Upro) were measured. The pathologic changes to the renal artery were observed by von-Kossa staining and the calcium content was detected by calcium assay kit. The pathologic changes to the kidney were observed by HE. Immunohistochemistry was applied to detect the protein expression of BMP2/Smad1/Runx2/Osterix signal pathway in the renal artery and real-time PCR were applied to detect the mRNA expression levels of BMP2 and Runx2. Results The calcium content and the deposition of black granules in DN group were significantly higher than those in group CON and lower than DN+VDN group at each time point (P＜0.05). The renal function indices in group DN and group DN+VDN were gradually increased in 8th,12th and 16th weeks, and were higher than those in group CON (P＜0.05). Compared with that in DN group, although the level of BUN, Scr, Cys C and 24-h Upro in DN+VDN group rats were higher at different time point, the level of Cys C at each time point and the level of 24-h Upro in the 16th week showed significant differences (P＜0.05). The pathological damages of the kidney in group DN and DN+VDN showed a continual worsening trend and the pathological changes of the kidney in group DN+VDN were more serious than those in group DN. Furthermore, the levels of BMP2/Smad1/Runx2/Osterix signal protein and BMP2, Runx2 mRNA in DN rats were higher than those in CON group, lower than DN+VDN group at each time point (P＜0.05). Correlation analysis demonstrated that calcium content was positively correlated with serum BUN, Scr, Cys C, 24-h Upro and the expression of BMP2, Runx2 mRNA (r=0.835, 0.705, 0.829, 0.897, 0.641, 0.683, P＜0.01, respectively). Conclusion Renal artery calcification may participate in and promote the progression of DN, and the BMP2 signal pathway may be an important regulating factor in DN with renal artery calcification.     

替米沙坦联合吡格列酮干预糖尿病肾病大鼠蛋白尿发生的机制

目的 观察替米沙坦联合吡格列酮对糖尿病肾病（DN）大鼠肾小球基底膜乙酰肝素酶（HPA）和足细胞podocin表达的影响，并探讨其可能机制。 方法 构建DN大鼠动物模型，将大鼠随机分为替米沙坦组（T组）、吡咯列酮组（B组）、替米沙坦+吡格列酮联合组（L组）、DN组（D组）及健康对照组（N组）。12 周后检测尿蛋白量（24 h）及血生化指标，用 RT-PCR和免疫组化检测HPA、podocin mRNA和蛋白的表达。 结果 灌胃12周后， L组尿蛋白量（24 h）显著低于T组、B组，差异有统计学意义（P ＜ 0.05）。与N组相比， T组、B组、L组、D组空腹血糖、相对肾质量、BUN、Scr均较高，差异有统计学意义（均P ＜ 0.05)。L组的Scr显著低于T组、B组，差异具有统计学意义（均P ＜ 0.05）。与N组相比，其余4组HPA蛋白表达较高， L组显著低于T组、B组；但其他4组podocin蛋白表达水平较低， L组显著高于T组、B组，差异均有统计学意义（均P ＜ 0.05）。与N组相比，其他4组HPA和podocin mRNA表达量较高，L组HPA mRNA表达显著低于T组、B组，podocin mRNA表达显著高于T组、B组，差异均有统计学意义（均P ＜ 0.05）。 结论 替米沙坦联合吡格列酮较单用药显著减轻DN大鼠早期蛋白尿，此作用可能通过下调DN肾小球基底膜HPA，上调足细胞podocin蛋白的表达实现。     

Effects of 12-lipoxygenase and angiotensinⅡ on p21, p27 and p57 in rat diabetic glomeruli

Objective To investigate the effects of 12-lipoxygenase (12-LO) and angiotensin Ⅱ(AngⅡ) on the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs) p21, p27 and p57 related to cell hypertrophy. Methods Mesangial cells were treated with high glucose for 24 hours and 48 hours respectively. 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] and AngⅡ were infused to rats by osmotic mini-pump for 1 week and 2 weeks respectively. Rats fed high fat diet were received low dose streptozotocin (STZ) to make type 2 diabetes (DN). The rats were divided into normal control group, DN group, DN+AngⅡ type 1 receptor blocker (ARB) group or 12-LO inhibitor (CDC) group. DN+ARB rats were treated by losartan for 6 weeks, and DN+CDC rats were treated for 8 weeks. Urine albumin and protein expressions of p21, p27 and p57 were detected by ELISA and Western blotting respectively. Glomeruli injury and expressions of p21 and p27 were detected by PAS staining and immunohistochemistry respectively. Results High glucose increased p21 and p27 protein expression in mesangial cells significantly compared with the relative control (all P＜0.05), but had no effect on p57. AngⅡ increased p27 protein expression in glomeruli significantly (P＜0.05), but had no effect on p21 and p57 protein expression. 12(S)-HETE increased both p21 and p27 protein expression in glomeruli significantly (all P＜0.05), but had no effect on p57 protein expression. Blood glucose, kidney/body weight, urinary protein, and glomerular p21 and p27 protein expressions were increased in DN group (all P＜0.05) compared with those in control group, with little change of p57 protein expression (P＜0.05). Moreover, glomerular hypertrophy and extra cellular matrix accumulation were observed in DN group. However, urine protein,kidney/body weight, renal injury, but not blood glucose, were decreased in DN+ARB group and DN+CDC group compared with DN group respectively (P＜0.05). Further DN+CDC rats had decreased both p21 and p27 protein expressions in glomeruli, but DN+ARB rats only had decreased p27 protein expression (all P＜0.05). Conclusions 12-LO may induce both p21 and p27 protein expression in DN glomeruli,but AngⅡ may induce only p27 expression.     

霉酚酸酯对糖尿病肾脏疾病大鼠肾组织中尾加压素Ⅱ及其受体的影响

目的探讨霉酚酸酯（MMF）对糖尿病肾脏疾病（diabetickidneydisease,DKD）大鼠肾组织中尾加压素Ⅱ（urotensinⅡ,UⅡ）蛋白与其受体UT表达和肾小球病理改变的影响。方法SD大鼠随机分为正常对照组、DKD组和MMF干预组,16周末测量24h尿蛋白定量、血糖、血肌酐、尿素氮。取肾脏标本测肾质量,部分肾组织行HE染色,光镜下观察肾小球组织形态学的改变,免疫组化观察UⅡ／UT表达。结果DKD大鼠肾组织中UⅡ／UT的表达增多。MMF能显著抑制大鼠24h尿蛋白的排泄,降低血肌酐、尿素氮;减轻肾脏病理改变,下调UⅡ／UT表达。结论UⅡ／UT的表达增多可能参与了DKD的发病过程。MMF对糖尿病大鼠肾脏的保护作用可能与下调肾组织中UⅡ／UT的表达水平有关。     

肾脏局部醛固酮对糖尿病肾病大鼠肾小管间质转分化的作用

目的 探讨醛固酮对糖尿病肾病（DN）大鼠肾小管间质转分化的影响。 方法 采用Wistar大鼠腹腔注射链脲菌素（STZ,60 mg/kg）制备糖尿病模型,4周后尿蛋白>30 mg/d为DN模型成功（n=16）,随机分为DN组（n=8）和螺内酯组（SP组,n=8）,以另8只正常大鼠作为对照组（N组）。SP组给予螺内酯40 mg&#8226;kg-1&#8226;d-1,N组、DN组每日以等量清水灌胃。8周后处死大鼠,收集尿、血浆、肾组织检测24 h尿蛋白定量、血肌酐和肾脏病理变化;用放射免疫法检测血浆、肾组织醛固酮浓度;用免疫组化、Western印迹方法检测E钙黏蛋白（E-cadherin）、α平滑肌肌动蛋白（α-SMA）蛋白的表达;用RT-PCR的方法检测E-cadherin、α-SMA mRNA的表达。 结果 与对照组比较,DN组尿蛋白排泄量、血肌酐均显著增加（均 P < 0.01）,肾组织E-cadherin蛋白和mRNA表达显著下调（均P < 0.01）,α-SMA蛋白和mRNA表达均显著上调（均P < 0.01）。DN组大鼠肾组织醛固酮显著升高[（24.71±5.30） ng/g比（16.38±2.85） ng/g,P < 0.01],与尿蛋白排泄量、血肌酐、α-SMA蛋白表达呈正相关（r = 0.737、0.574、0.688,均P < 0.05）,与E-cadherin蛋白表达呈负相关（r = －0.659,P < 0.01）。各组间血清醛固酮含量差异无统计学意义。与DN组比较,SP组大鼠尿蛋白排泄和血肌酐显著下降（均P < 0.01）,E-cadherin蛋白和mRNA表达上调（均P < 0.05）,而α-SMA蛋白和mRNA表达显著下调(均P < 0.01)。 结论 DN大鼠肾组织局部醛固酮参与了糖尿病肾病肾间质转分化,螺内酯可以阻断醛固酮与其受体结合,抑制肾小管间质转分化,从而起到肾脏保护作用。     

尾加压素Ⅱ在糖尿病肾病大鼠动脉粥样硬化形成的表达及黄芪的干预

目的:观察糖尿病肾病大鼠主动脉、肾脏组织中尾加压素Ⅱ(urotensinⅡ,UⅡ)及其G蛋白耦联受体14(G-protein-coupled receptor14,GPR14)水平的变化,探讨UⅡ在糖尿病肾病动脉硬化形成的作用和发病机制及黄芪的干预效果。方法:采用高糖高脂饮食和链脲佐菌素(STZ)腹腔注射法建立大鼠糖尿病肾病模型。将大鼠分为正常对照组(NC)、糖尿病肾病组(DN)、黄芪治疗组(HZ)(予黄芪注射液5ml/kg灌胃)。于14周末处死动物,常规病理学检查,免疫组化观察UⅡ、GPR14蛋白表达;RT-PCR观察UⅡmRNA表达。结果:与NC组比较,DN组主动脉、肾组织UⅡ、GPR14表达增加,肾组织UⅡmRNA表达增加(P<0.01);与DN组比较,HZ组表达显著减少(P<0.05)。结论:UⅡ及其受体GPR14的高表达提示其在糖尿病肾病动脉粥样硬化形成的过程中可能起重要作用;黄芪能够缓解肾脏病理损伤,其机制可能是通过抑制UⅡ和GPR14异常表达有关。     

Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney

Objectives Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. The NO system has been implicated in the pathogenesis of DN. In this study, we aimed to evaluate the healing effect of pentoxifylline on NOS in STZ-induced diabetic rat’s kidney. Material and methods In this study, 50 Wistar albino male rats were used. The rats were divided into five groups; Group C control; Group D only diabetes; Group D?+?PI and D?+?PII diabetes?+?pentoxifylline; Group P only pentoxifylline. Group DPI rats received just pentoxifylline from the beginning of the experiments. However, Group DPII rats received saline in the first month and 50?mg/kg/day of pentoxifylline for the following month. At the end of two months, NOS expressions in kidney tissue were assessed using qRT-PCR and immunohistochemistry analysis. Results At the end of the experiments, desquamation of the epithelial cells of the tubules, clear glycogen-filled distal tubules and increased number of apoptotic cells were seen in Group D. Diabetic rats’ nNOS immunoreactivity had increased and eNOS and iNOS immunoreactivity had decreased; nNOS, iNOS and eNOS mRNA levels tended to decrease compared to the control group. PTX ameliorated eNOS, iNOS and nNOS protein levels and apoptotic cells, but did not affect mRNA levels. Conclusion In conclusion, PTX has a healing effect on this damage by affecting NOS expression.     

益肾胶囊对糖尿病肾病大鼠肾组织JAK/STAT信号通路的影响

目的：观察益肾胶囊对糖尿病肾病（DN）大鼠肾组织JAK/STAT信号通路影响,探讨益肾胶囊对DN大鼠肾脏保护作用的可能机制。方法：将Wistar大鼠制备成DN模型。随机分为4组,即正常对照组（N组）、DN模型组（DN组）、益肾胶囊治疗组（625mg·kg-1.d-1）、氯沙坦钾治疗组（30mg·kg-1.d-1）。实验周期12周。期间检测大鼠血糖和24h尿蛋白定量,通过光镜及电镜观察肾脏组织病理形态学的变化;采用免疫组化方法检测肾组织磷酸化JAK2（p-JAK2）、磷酸化STAT3（p-STAT3）表达及转化生长因子β1（TGF-β1）表达变化。结果：12周末,DN组大鼠肾组织中p-JAK2、p-STAT3、TGF-β1表达显著高于同期正常对照组（P〈0.05）。益肾胶囊治疗组和氯沙坦钾治疗组肾组织中p-JAK2、p-STAT3、TGF-β1表达显著低于同期DN组（P〈0.05）;24h尿蛋白定量显著低于同期DN组（P〈0.05）;病理损伤较同期DN组改善。结论：益肾胶囊可能部分通过抑制DN大鼠肾组织JAK/STAT通路调节肾组织TGF-β1表达,发挥对DN大鼠肾脏的保护作用。     

Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711)

BACKGROUND: Alagebrium (ALT-711) has been shown to improve renal dysfunction in animal models of diabetes. METHODS: To test its effects in diabetic nephropathy (DN), ALT-711 was administered (1 mg/kg daily i.p.) to 9-week-old female db/db mice (n = 15, group A1) for 3 weeks and to 3-month-old (n = 15, group A2), 7-month-old (n = 7, group A3), and 12-month-old (n = 5, group A4) female db/db mice for 12 weeks, while a similar number of diabetic and nondiabetic mice were used as controls. The epsilonN-carboxymethyllysine (CML) levels in serum, urine, skin, and kidney tissue were measured by enzyme-linked immunosorbent assay. The renal morphometric parameters were assessed by electron and light microscopy. RESULTS: By the 3rd week of treatment, the serum CML level decreased by 41%, and the urinary CML concentration increased by 138% from baseline, while the urinary albumin/creatinine ratio was lower (p < 0.05) in diabetic and nondiabetic group A1 mice. After 3 months of treatment, serum, skin, and kidney CML levels and urinary albumin/creatinine ratio were lower (p < 0.05) and the urinary CML levels higher (p < 0.05) in treated group A2, A3, and A4 animals compared with groups which received phosphate-buffered saline, with a similar pattern observed in nondiabetic mice. The renal morphological parameters characteristic of DN decreased in treated compared with untreated mice. CONCLUSION: Alagebrium may prevent, delay, and/or reverse established DN in db/db mice by reducing the systemic advanced glycation end product pools and facilitating the urinary excretion of advanced glycation end products.     

来氟米特对糖尿病大鼠肾脏Podocalyxin表达的影响

目的：研究来氟米特对糖尿病大鼠肾脏Podocalyxin蛋白表达的影响。方法：48只雄性Wistar大鼠随机分为正常对照组、糖尿病肾病模型组、来氟米特干预组、氯沙坦干预组,每组12只。腹腔注射STZ建立糖尿病肾病大鼠模型,给予药物干预。观察各组大鼠血糖、24h尿微量白蛋白量的变化,8周、12周末各组大鼠血尿素氮（BUN）、肌酐（Scr）、肾脏组织病理变化及肾组织Podocalyxin表达水平。结果：8周、12周末模型组、来氟米特干预组、氯沙坦干预组24h尿微量白蛋白定量较正常对照组显著增高（P〈0.05）,肾组织病理损伤明显,大鼠Podocalyxin蛋白表达均显著低于正常对照组（P〈0.05）。8周、12周末干预组24h尿微量白蛋白定量、BUN、Scr水平显著低于同期模型组（P〈0.05）,肾组织病理损伤较模型组明显减轻,大鼠肾组织Podocalyxin蛋白表达显著高于同期模型组（P〈0.05）。结论：来氟米特能够上调糖尿病大鼠肾组织Podocalyxin表达水平,对糖尿病肾脏损伤有保护作用。     

滋肾活血法干预实验性DN模型大鼠的实验研究

目的:观察滋肾活血法(活血降糖胶囊)对实验性糖尿病肾病(diabetic nephropathy,DN)模型大鼠的肾脏保护作用。方法:取SD雄性大鼠,予部分肾切除合并单次小剂量腹腔注射STZ,同时给予隔日高脂饲料建造DN动物模型,筛选DN成模大鼠,随机分成模型(DNM)组、中药(HX)组、西药(IR)组并随机设正常对照(NC)组,分别予中西药物干预;8周后处死大鼠,检测尿蛋白、血糖、肾功能、血脂,电镜及光镜观测肾脏超微病理结构变化,测量肾小球截面积(MGA)、细胞外基质截面积(MMA)、肾小球基底膜厚度(GBM),计算细胞外基质截面积/肾小球截面积(MMA/MGA)比值及肾小球硬化指数(GSI)。结果:HX组大鼠24h尿蛋白定量、GSI、GBM、MMA/MGA比值较DNM组均明显降低(P<0.01),光镜、电镜示病理损害较DNM组改善。HX组血脂较IR组、DNM组降低(P<0.05或P<0.01)。结论:滋肾活血中药复方活血降糖胶囊可减轻实验性DN模型大鼠蛋白尿及肾脏损害,改善脂质代谢,发挥肾脏保护作用。     

MCP-1、ICAM-1在糖尿病肾病大鼠肾脏损害中作用及厄贝沙坦干预的影响

目的：探讨MCP-1、ICAM-1在糖尿病肾病大鼠肾脏损害中作用及厄贝沙坦对二者的影响.方法：采用高糖高脂饮食合并链脲佐菌素腹腔注射的方法建立糖尿病肾病大鼠模型.将大鼠随机分为正常对照NC 组、糖尿病肾病DN组、厄贝沙坦DI组,检测各组大鼠24 h尿量、24 h尿白蛋白定量（24 h UTP）、血糖（BG）、血肌酐（Scr）、尿素氮（BUN）、肾重指数（KI）;行HE染色观察各组大鼠病理学形态,免疫组化观察MCP-1、ICAM-1蛋白的表达,RT-PCR观察MCP-1 mRNA、ICAM-1mRNA的表达.结果：与NC组比较,DN组大鼠肾脏病理改变加重,24 h尿量、24 h UTP、KI、BG、Scr、BUN、肾脏组织中MCP-1mRNA和ICAM-1mRNA及蛋白水平均显著增加,差异均有统计学意义（P＆lt;0.01）;与DN组比较,DI组大鼠BG、BUN、Scr有所改善,差异无统计学意义;肾脏病理改变减轻,其余指标明显降低,差异有统计学意义（P＆lt;0.05）.结论：MCP-1、ICAM-1在糖尿病肾病肾脏损害过程中可能起重要作用;厄贝沙坦能够减轻糖尿病肾病肾组织MCP-1、ICAM-1的表达,缓解了肾脏病理损伤.     

氯沙坦钾对糖尿病肾病大鼠肾组织p-JAK2、p-STAT3及VEGF表达的影响

目的：探讨氯沙坦钾对糖尿病肾病（diabetic nephropathy,DN）大鼠肾组织 p - JAK2、p - STAT3及 VEGF 表达的影响。方法：健康雄性 SD 大鼠30只随机分为正常对照组（C 组）、DN 模型组（DN 组）、氯沙坦钾组（L 组）。采用单次腹腔内注射链脲佐菌素（streptozotocin,STZ）法建立 DN 大鼠模型,周期12周。实验12周末检测大鼠血糖、Scr、BUN、24 h 尿蛋白定量;光镜及电镜下观察大鼠肾组织病理改变;采用免疫组化方法检测大鼠肾组织 p - JAK2、p - STAT3、VEGF 表达。结果：实验12周末,模型组大鼠血糖、Scr、BUN、24 h 尿蛋白定量均高于对照组（P ﹤0．05）,肾组织中 p - JAK2、p - STAT3、VEGF 表达均高于对照组（P ﹤0．05）;氯沙坦钾组大鼠 Scr、BUN、24 h 尿蛋白定量均低于模型组（P ﹤0．05）,肾组织 p - JAK2、p -STAT3、VEGF 表达均低于模型组（P ﹤0．05）。结论：氯沙坦钾可能部分通过调控 p - JAK2、p - STAT3及 VEGF 的表达而发挥肾脏保护作用。