霉酚酸酯对糖尿病大鼠肾脏的保护作用

目的探讨霉酚酸酯(MMF)对糖尿病模型大鼠肾脏的保护作用及其机制。方法SD大鼠随机分为3组:对照组、糖尿病模型组和糖尿病治疗组。治疗12周后,检测大鼠血糖(BG)、血尿素氮(BUN)、血肌酐(Scr)、肾肥大指数(肾重KW/体重BW)、肌酐清除率(Ccr)和24h尿蛋白(24Upro)。肾组织做常规光镜和电镜检查。用免疫组织化学方法检测肾组织中细胞间黏附分子-1(ICAM-1)和增殖细胞核抗原(PCNA)蛋白的表达,半定量RT-PCR的方法检测肾组织中ICAM-1mRNA的表达。结果与对照组相比,糖尿病组大鼠BG、KW/BW、24Upro、BUN、Scr和Ccr均显著升高(P<0.05或0.01);系膜密度和肾小球基底膜厚度均显著增加(P<0.01);肾组织内ICAM-1和PCNA的蛋白质表达及ICAM-1的mRNA表达均显著上调(P<0.05或0.01)。除血糖外,治疗组上述指标均显著回降(P<0.05或0.01)。结论MMF对糖尿病肾病有保护作用,其机制可能与下调ICAM-1和PCNA的表达有关。     

骨调素和巨噬细胞集落刺激因子在糖尿病大鼠肾组织中的表达及霉酚酸酯的干预作用

目的：研究骨调素(OPN)和巨噬细胞集落刺激因子（M-CSF)在糖尿病大鼠肾组织中的表达及免疫抑制剂霉酚酸酯（MMF）的干预作用,旨在探讨MMF对糖尿病肾病(DN)的保护作用及机制。方法:Wistar大鼠行右肾切除术2周后,随机分为右肾切除对照组(NC)、糖尿病组(DM)、霉酚酸酯治疗组(DM+MMF)。腹腔注射链脲佐菌素(STZ,65mg/kg)诱发糖尿病模型,MMF15mg·kg-1·d-1灌胃。检测各组8周末的左肾重/体重比值、24h尿蛋白（Upro）、血糖(BG)、血肌酐(Scr),观察肾脏形态学变化,免疫组化检测肾组织中OPN、M-CSF及CD68表达,荧光实时定量PCR测定肾组织中OPNmRNA表达。结果:与对照组相比,DM组大鼠血糖、Upro、肾重/体重比值均显著上升(P<0.01);肾间质纤维化面积扩大(P<0.01);肾组织内OPN、M-CSF、CD68表达及OPNmRNA的表达均显著上调(P<0.01)。MMF干预后,上述指标除血糖外均被明显抑制(P<0.05或P<0.01)。结论:MMF减少糖尿病大鼠肾组织中OPN、M-CSF、CD68及OPNmRNA的表达,降低蛋白尿,预防肾损伤。MMF明显抑制DN肾小管－间质损害,可能与其抑制巨噬细胞的趋化与增殖有关。     

内源性硫化氢在糖尿病肾病病理变化中的作用

目的：观察糖尿病肾病（DN）大鼠肾组织中α-平滑肌肌动蛋白（α-SMA）分布及含量的变化,探讨内源性H2S在糖尿病肾病病理变化中的作用。方法:雄性SD大鼠28只随机分为：对照组、DN组、H2S干预组、胱硫醚-γ-裂解酶(CSE)阻断剂组。采用免疫组织化学法及Western免疫印迹法,检测各组大鼠肾脏组织中α-SMA的分布及含量。结果:(1)对照组大鼠肾脏中的α-SMA主要存在于血管壁,DN组、CSE阻断剂组除血管壁外,肾小球系膜区及肾间质均有表达;H2S干预组的DN大鼠肾脏中α-SMA的表达与对照组相似,主要位于血管壁。(2)与对照组比较,DN组中α-SMA的含量增加［DN组(40209±935)vs对照组(16028±958),P<0.01］;与DN组及CSE阻断剂组比较,H2S干预组中α-SMA的含量下降［H2S干预组(23612±510)vsDN组(40209±935)、CSE阻断剂组(39338±1342),P<0.01］。结论:内源性H2S可抑制DN大鼠肾脏中成肌纤维细胞的生成,延缓糖尿病肾病的病理改变。     

碱性成纤维细胞生长因子对大鼠实验性肾小管损伤和间质病变的作用

研究碱性成纤维细胞生长因子在大鼠肾小管损伤,再生以及肾间质病变过程中的作用。方法应用Ｎｏｒｔｈｅｒｎ印迹杂交,原位杂交及免疫组织化学ＳＰ方法,观察在大鼠的庆大霉素中毒肾小管损伤和再生过程,。ｂＦＧＦ及其受体表达的情况,＾３Ｈ－ＴｄＲ掺入法检测ｂＦＧＦ对培养的肾小管上皮细胞和肾间质成纤维细胞增殖的影响。结果肾小管上皮细胞损伤和再生过程中,ｂＦＧＦ ｍＲＮＡ有表达,随着修昨的增强,表达量逐渐增高;同时     

LOX-1在2型糖尿病大鼠肾小管间质中的表达及其意义

 目的：探讨血凝素样氧化低密度脂蛋白受体1（LOX-1）在糖尿病肾病（DN）中的作用及其机制。方法：SD大鼠随机分为正常对照组和糖尿病模型组。以高脂高糖饮食加低剂量注射链脲佐菌素复制2型糖尿病大鼠模型。动态观察：生化指标和24 h尿白蛋白排泄率（UAER）;苏木素伊红（HE）和过碘酸-雪夫反应（PAS）染色观察肾脏病理,免疫组化检测LOX-1和转化生长因子β1（TGF-β1）蛋白表达,荧光定量聚合酶链反应检测LOX-1和TGF-β1 mRNA表达,ELISA检测血清单核细胞趋化因子-1（MCP-1）、细胞间黏附分子（ICAM）和肿瘤坏死因子α（TNF-α）的浓度。结果：随着造模时间的延长,血清中总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）含量和UAER逐渐升高,高密度脂蛋白（HDL）在成模时升高,但随着病变进展含量减少;LOX-1和TGF-β1在肾小管中蛋白表达增加;与正常组比较,模型各组LOX-1和TGF-β1蛋白和mRNA表达逐渐增加;与正常组比较,模型各组血清MCP-1、ICAM和TNF-α水平均增高;LOX-1 mRNA表达与UAER、TNF-α和TGF-β1 mRNA表达量之间呈正相关（r值分别为0.509、0.649和0.800）（P<0.05）。结论：LOX-1在2型糖尿病肾小管中表达增加,使肾小管损伤,其作用可能通过炎症因子释放和炎症细胞浸润而实现,提示其在DN发生和发展过程中起重要作用。     

水飞蓟素对大鼠肾小管间质纤维化的影响及其作用机制探讨

目的:探讨水飞蓟素对大鼠肾间质纤维化的作用及对内皮素-1(ET-1)及内皮素A受体(ETaR)表达的影响.方法:72只SD大鼠随机分为三组, 即假手术组、模型组、水飞蓟素治疗组.以单侧输尿管结扎术建立输尿管梗阻的动物模型.治疗组给予水飞蓟素每日30 mg/kg灌胃, 模型组和假手术组给予生理盐水灌胃.各组分别于实验第7、14、21天各收获大鼠8只, 进行肾组织病理学观察.用免疫组化方法检测肾组织ET-1及ETaR的表达.结果:治疗组肾小管间质积分较模型组明显减轻;肾组织表达ET-1及ETaR在治疗组也较模型组明显减少.结论:水飞蓟素可能是通过下调ET-1及ETaR表达而抑制纤维化的发生, 从而起到对肾脏的保护作用.     

红景天抑制阿霉素肾病大鼠肾小管间质α平滑肌肌动蛋白表达

目的探讨红景天对阿霉素肾病大鼠肾小管上皮细胞表型转化的作用。方法用阿霉素诱导制成大鼠肾病模型,红景天治疗组第4周起喂服诺迪康胶囊[即圣地红景天0.672g/(kg.d)],对照组及肾病组喂水[3mL/(kg.d)],于第4、8、12、16和20周末分批处死大鼠,观察肾组织病理变化,检测肌成纤维细胞(MFB)的标记蛋白α平滑肌肌动蛋白(α-SMA)在肾小管间质中的表达。结果16周肾病组大鼠肾小管间质α-SMA半定量为6.24±0.57,明显高于红景天治疗组3.84±0.28(P<0.01),且与小管间质损害程度相关(r=0.872,P<0.01)。结论红景天能抑制肾小管间质细胞表型转化,对肾间质的纤维化有较好的防治作用。     

白蛋白超载诱导近端肾小管上皮细胞表达α-平滑肌肌动蛋白

目的：探讨白蛋白超载是否可以诱导近端肾小管上皮细胞（PTCs）向成肌纤维细胞转化（EMT）。方法：大鼠近端肾小管上皮细胞株NRK52E培养至70％融合或完全融合时，用不同浓度（0-30 g/L）去脂牛血清白蛋白(dBSA)超载144 h。NRK52E形态和结构改变用光镜和电镜观测。上皮细胞标记抗原E-钙黏蛋白和β-连环蛋白，以及成肌纤维细胞标记抗原α-平滑肌肌动蛋白（α-SMA）表达用免疫荧光和Western 印迹法检测。结果：dBSA超载可诱导未完全融合NRK52E表达α-SMA，少数细胞变为长梭形，但α-SMA 的表达不呈剂量依赖性。dBSA超载处理不能诱导完全融合的NRK52E表达α-SMA，细胞形态也无改变。dBSA超载完全或未完全融合NRK52E均不能抑制E-钙黏蛋白和β-连环蛋白表达，电镜显示这些细胞仍保持上皮细胞结构，包括微绒毛和紧密连接。结论：白蛋白超载可以诱导PTCs表达α-SMA，促进EMT，但不能诱导PTCs完全转化为成肌纤维细胞，细胞完全融合可抑制白蛋白超载诱导PTCs表达α-SMA。     

真武汤对链脲佐菌素所致大鼠糖尿病肾病的保护作用

目的：探讨真武汤对糖尿病大鼠肾脏的保护作用及机制。方法：腹腔注射链脲佐菌素(STZ)建立糖尿病肾病大鼠模型,将成模大鼠随机分为糖尿病肾病(DN)模型组和真武汤治疗组（真武组）,另设正常组。采用生化、HE染色观察真武汤对糖尿病肾病大鼠肾功能、肾组织形态学变化及脂质过氧化相关参数的作用;采用蛋白免疫印迹方法探讨真武汤对肾组织α-平滑肌肌动蛋白（α-SMA）和NF-κB表达的影响。结果：模型组大鼠肾系数、24h尿蛋白定量、血尿素氮、肌酐、血糖和丙二醛(MDA)均显著升高(P<0.05),体重、超氧化物歧化酶(SOD)及诱导型一氧化氮合酶（iNOS）显著降低(P<0.05);真武组大鼠的肾系数、24h尿蛋白、尿素氮、肌酐、血糖和MDA明显低于模型组(P<0.05),iNOS显著高于模型组（P<0.05）;模型组大鼠肾小球肥大、毛细血管基底膜增厚,系膜基质增生,肾小管上皮细胞空泡样变,可见蛋白管型;真武组病变轻于模型组。模型大鼠肾组织α-SMA及NF-κB蛋白的水平明显高于正常组（P<0.05）,真武组大鼠肾组织α-SMA及NF-κB蛋白水平明显低于模型组（P<0.05）。结论：真武汤能减轻糖尿病肾病肾脏局部氧化应激反应,改善糖尿病肾病大鼠肾功能,减轻病理损伤,其发挥肾脏保护作用可能与抑制α-SMA及NF-κB蛋白的表达有关。     

环磷酰胺与霉酚酸酯对IgA肾病患者疗效及安全性对比

目的:探讨环磷酰胺与霉酚酸酯应用于IgA肾病患者中的疗效及安全性。方法:选取我院2018年3月至2019年1月收治的101例IgA肾病患者,使用简单随机化法将其分为试验组(51例)和对照组(50例)。对照组患者用环磷酰胺治疗,试验组患者用霉酚酸酯治疗。治疗6个月后,比较两组临床效果,使用比色法测量患者血尿酸,使用酶联免疫吸附法测量患者肾损伤指标肾损伤分子-1(Kidney injury molecule 1,KIM-1)、尿液中性粒细胞明胶酶相关载脂蛋白(Neutrophil gelatinase-associated lipoealin,NAGL)、N-乙酰-β-D氨基葡萄糖苷酶(N-acetylbeta-glucosaminidase,NAG)水平及不良反应的发生情况。结果:试验组患者治疗后总有效率为92.16%,而对照组为96.00%,组间比较差异无统计学意义(P0.05);血尿酸、KIM-1、NAGL、NAG组间比较,差异无统计学意义(P0.05)。但试验组患者不良反发生率明显低于对照组(P0.05)。结论:环磷酰胺与霉酚酸酯对IgA肾病患者疗效相当,但霉酚酸酯治疗后不良反应发生率更低。     

肾病综合征大鼠模型的建立及酶酚酸酯对其作用的实验研究

目的：研究酶酚酸酯（ＭＭＦ）对大鼠肾病综合征的治疗作用。为临床应用提供依据。方法：经尾静脉一次性注射阿霉素,构建大鼠肾病综合征动物模型。观察ＭＭＦ对大鼠肾病综合征血、尿生化指标、淋巴细胞电压依赖性钾通道及肾脏组织学改变的影响。并与强的松进行对照研究。结果：注射阿霉素１４ｄ。大鼠肾病综合征模型建立。模型鼠表现外周Ｔ淋巴细胞电压依赖性钾通道电流增强。ＭＭＦ治疗可使大鼠尿蛋白和血尿素氮明显下降。血白蛋白上升。肾脏病理显示足突无明显融合。疗效明显优于强的松治疗组。结论：在阿霉素诱导的大鼠肾病综合征模型的形成中,细胞免疫参与了其发病,ＭＭＦ能明显改善模型鼠的肾功能并减轻肾脏组织形态学损害。且疗效优于强的松。     

Histological changes after the use of mycophenolate mofetil in autoimmune hepatitis

Corticosteroids and azathioprine are considered standard treatment for autoimmune hepatitis. There are, however, well-known systemic side effects that may preclude continuation with these immunosuppressive therapies, and small trials of the anti-metabolite mycophenolate mofetil have been reported. We report liver biopsy findings in a follow-up biopsy of a patient who had been switched from azathioprine to mycophenolate mofetil for treatment of presumed, steroid-responsive autoimmune hepatitis. Both cytoplasmic features of adaptation and nuclear alterations were noted in hepatocytes. Possible mechanisms for these findings are discussed.     

The immunosuppressive drug mycophenolate mofetil impairs the adhesion capacity of gastrointestinal tumour cells

Immunosuppression correlates with the development and recurrence of cancer. Mycophenolate mofetil (MMF) has been shown to reduce adhesion molecule expression and leucocyte recruitment into the donor organ. We have hypothesized that MMF might also prevent receptor-dependent tumour dissemination. Therefore, we have investigated the effects of MMF on tumour cell adhesion to human umbilical vein endothelial cells (HUVEC) and compared them with the effects on T cell-endothelial cell interactions. Influence of MMF on cellular adhesion to HUVEC was analysed using isolated CD4+ and CD8+ T cells, or WiDr colon adenocarcinoma cells as the model tumour. HUVEC receptors ICAM-1, VCAM-1, E-selectin and P-selectin were detected by flow cytometry, Western blot or Northern blot analysis. Binding activity of T cells or WiDr cells in the presence of MMF were measured using immobilized receptor globulin chimeras. MMF potently blocked both T cell and WiDr cell binding to endothelium by 80%. Surface expression of the endothelial cell receptors was reduced by MMF in a dose-dependent manner. E-selectin mRNA was concurrently reduced with a maximum effect at 1 microm. Interestingly, MMF acted differently on T cells and WiDr cells. Maximum efficacy of MMF was reached at 10 and 1 microm, respectively. Furthermore, MMF specifically suppressed T cell attachment to ICAM-1, VCAM-1 and P-selectin. In contrast, MMF prevented WiDr cell attachment to E-selectin. In conclusion, our data reveal distinct effects of MMF on both T cell adhesion and tumour cell adhesion to endothelial cells. This suggests that MMF not only interferes with the invasion of alloactivated T cells, but might also be of value in managing post-transplantation malignancy.     

Improved gastrointestinal symptoms and quality of life after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant patients receiving tacrolimus

It is reported that a conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) relieves gastrointestinal (GI) symptom burden and improves health-related quality of life (HRQoL). However, it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion. In this prospective, multi-center, open-label trial, patients were categorized into two groups by their GI symptom screening. Equimolar EC-MPS (n=175) was prescribed for patients with GI burdens; those with no complaints remained on MMF (n=83). Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) were evaluated at baseline and after one month. Patients and physicians completed Overall Treatment Effect (OTE) at one month. EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients (all P<0.001). Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month, but MMF-continued patients showed worsened GSRS scores (all P<0.05). OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did (P<0.001). In tacrolimus-treated renal transplant recipients with GI burdens, a conversion from MMF to EC-MPS improves GI-related symptoms and HRQoL.     

高果糖饮食对大鼠肾脏的毒性作用

 [摘要] 目的　观察高果糖饮食诱导的高甘油三酯血症对大鼠肾组织病理形态的影响,探讨脂质肾毒性的作用机制。方法 将32只大鼠分为正常对照组(N组,n=16)及高果糖组(F组,n=16),8及16周时分批处死,检测各组大鼠的肾功能、空腹血糖、血脂及24h尿微量白蛋白;检测大鼠肾皮质甘油三酯含量;采用免疫组化分析IV型胶原及α-平滑肌动蛋白表达和定位,并观察肾脏病理变化。电镜观察肾脏基底膜变化。结果　8周和16周时,高果糖组血中甘油三酯分别达(1.65+0.86)mmol/L、（2.13+0.87）mmol/L,极低密度脂蛋白分别达(0.75+0.39)mmol/L、(0.97+0.40)mmol/L,肾组织中甘油三酯分别达(7.21+2.20)mg/g、(7.92+3.05)mg/g,24h尿微量白蛋白分别达(63.00+12.00)μg、(150.00+48.00) μg,较对照组明显升高（P<0.05）;肾脏病理改变加重,基底膜增厚,肾组织IV型胶原α-SMA表达明显增加（P<0.05）。结论　高果糖饮食可诱导大鼠高甘油三酯血症,并使肾组织油三酯水平增加导致肾脏损伤。     

肾动脉钙化增加2型糖尿病肾病大鼠进行性肾功能损伤

目的探讨肾动脉钙化对2型糖尿病肾病大鼠肾功能的影响。方法将大鼠随机分为对照组(CON组)、糖尿病肾病组(DN组)及DN合并肾动脉血管钙化组(DN+VC组)。DN组和DN+VC组大鼠在高脂高糖饮食基础上腹腔注射链脲菌素(STZ)制备2型糖尿病肾病(diabetic nephropathy,DN)大鼠模型,造模成功后DN+VC组肌注维生素D3及尼古丁灌胃,分别于实验第8、12和16周末处死大鼠,用Von Kossa染色观察大鼠肾动脉钙盐沉积,Ca2+试剂盒检测肾动脉钙含量,免疫荧光双染观察肾动脉α-SMA/BMP2表达,荧光定量PCR检测肾动脉BMP2 mRNA水平等判断肾动脉钙化程度。检测大鼠血清尿素氮、肌酐、胱抑素C及24 h尿蛋白水平,HE染色观察肾组织病理改变。结果 DN组及DN+VC组肾动脉的钙盐沉积及钙含量、BMP2蛋白及基因表达均较同时间点CON组明显增加,DN+VC组较DN组增加更明显(P0.05)。DN组和DN+VC组大鼠血清尿素氮、肌酐、胱抑素C及24 h尿蛋白随时间进展逐渐升高,且明显高于同时间点CON组(P0.05)。与DN组相比,DN+VC组大鼠仅胱抑素C水平明显升高(P0.05),24 h尿蛋白量在第16周时明显增加(P0.05)。DN组大鼠肾组织病理损伤呈进行性加重,DN+VC组大鼠的病理改变较DN组明显加重。肾动脉钙含量与血清尿素氮、肌酐、胱抑素C、24 h尿蛋白以及BMP2 mRNA呈正相关(P0.01)。结论肾动脉钙化的发生及严重程度可能参与和促进糖尿病肾病的进展。     

Renoprotective effects of combination of angiotensin converting enzyme inhibitor with mycophenolate mofetil in diabetic rats

Objective and design Previously it was shown that blocking of the renin-angiotensin system (RAS) by angiotensin converting enzyme (ACE) inhibitors, or suppression of inflammatory responses by immunosuppressive drugs such as mycophenolate mofetil (MMF) could attenuate renal injury in diabetic rats. Whether RAS blockade combined with an immunosuppressive drug provides superior renoprotection against diabetic nephropathy has not been clearly delineated. Materials Diabetes was induced by injection of streptozotocin after uninephrectomy. Treatment Rats were randomly separated into five groups: control, diabetes, diabetes treated with enalapril (an ACE inhibitor, 10 mg/kg/d by gastric gavage), diabetes treated with MMF (10 mg/kg/d by gastric gavage), or diabetes treated with a combination of both agents and were followed for 8 weeks. Methods 24 h urinary albumin excretion rate (AER) was determined, renal injury was evaluated, immunohistochemistry for ED-1 macrophage marker, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were performed, and expression of transforming growth factor (TGF)-β1 protein was determined by Western blotting analysis. Results Diabetes was associated with a considerable increase in AER. Both enalapril and MMF retarded the increase in albuminuria, which was nearly completely abrogated by combination therapy. Increased glomerular volume and tubulointerstitial injury index in diabetic rats was attenuated by treatment with either enalapril or MMF and further reduced by the combination of the two. Elevated malondialdehyde levels in renal tissue were reduced by enalapril or MMF and, more effectively, by combined enalapril with MMF. Renal overexpression of ICAM-1 was not retarded by enalapril and attenuated by MMF or combined enalapril with MMF. Combination therapy was associated with a superior suppression of diabetes-induced macrophage recruitment and overexpression of MCP-1 and TGFβ1 compared to either monotherapy in renal tissue. Conclusion The combination of enalapril and MMF confers superiority over monotherapy in renoprotection, a mechanism which may be at least partly correlated with synergistic suppression of increased macrophage recruitment and overexpression of MCP-1 and TGF-β1 in renal tissue in diabetic rats. Received 26 July 2005; returned for revision 5 October 2005; returned for final revision 9 January 2006; accepted by M. Katori 23 January 2006     

丹参联合黄芪对糖尿病肾病大鼠肾脏线粒体呼吸及能量代谢的影响

目的:探讨丹参联合黄芪对糖尿病肾病(DN)大鼠肾脏功能及线粒体呼吸和能量代谢的影响。方法:选择健康SD大鼠,使用链脲佐菌素制作DN大鼠模型,按随机数字表法分为DN模型组(DN组)、丹参注射液干预组(丹参组)、黄芪注射液干预组(黄芪组)、丹参联合黄芪注射液干预组(联合组)和正常对照组(对照组),每组各8只。丹参组加予丹参注射液灌胃,黄芪组加予黄芪注射液灌胃,联合组加予丹参联合注射液灌胃,正常组和DN组同时给予等量的生理盐水,连续喂养6周。检测空腹血糖、血尿素氮、血清肌酐、24小时尿量及尿蛋白定量,留取肾组织,高效液相色谱法检测ATP、ADP、AMP,提取线粒体,氧电极法检测线粒体3态呼吸速率(T3)、4态呼吸速率(T4)和呼吸控制率(RCR)。结果:与DN组大鼠比较,丹参组、黄芪组和联合组大鼠的血糖水平、血尿素氮、血清肌酐、尿蛋白定量下降,24 h尿量增加,肾脏组织线粒体T3和RCR升高,ATP、ADP含量增加,P均<0.05。但联合组与丹参组和黄芪组对比,各项指标无显著差异。结论:丹参和黄芪单用及联合可能通过改善DN大鼠肾脏线粒体呼吸功能及能量代谢,改善DN大鼠肾脏的功能。丹参联合黄芪组较单纯丹参或单纯黄芪无显著优势。     

Melatonin and/or rowatinex attenuate streptozotocin-induced diabetic renal injury in rats

The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (TAC), kidney injury molecule-1 (KIM-1), heat shock protein-70 (HSP-70), caspase-3, transforming growth factor β1 (TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.