白花丹参对D-半乳糖致小鼠氧化应激的影响

目的研究白花丹参制剂的抗氧化应激作用。方法用D-半乳糖造氧化应激小鼠模型,同时分别灌胃给予不同剂量的白花丹参水提物,观察其对氧化应激模型小鼠脑组织和肾脏自由基及抗氧化酶的影响。结果氧化应激小鼠脑组织和肾脏中丙二醛(malondialdehyde,MDA)和活性氧(reactive oxygen species,ROS)升高、超氧化物歧化酶(superoxide dismutase,SOD)及总抗氧化活力(total antioxidation capability,T-AOC)下降。分别灌胃给予10、20、40g·kg-1·d-1白花丹参生药的水提物,能使氧化应激模型小鼠脑内和肾脏内MDA及ROS下降;SOD及T-AOC活力提高。结论白花丹参水提物有抗氧化应激作用,其机制与清除自由基及增加内源性抗氧化酶活力有关。     

卡维地洛减轻顺铂的肾损害

目的：研究顺铂肾损害中肾小管上皮细胞凋亡情况；以卡维地洛干预，探讨Bax、Bcl-2在其中的作用及机制。方法:雄性Wistar大鼠随机分为生理盐水（NS）对照组、卡维地洛对照组、顺铂组、卡维地洛治疗组。测定血清尿素氮（BUN）、肌酐（SCr）、肾组织中丙二醛（MDA）、抑制羟自由基能力(IHR)；过碘酸-希夫氏碱（PAS）染色观察肾脏病理改变；原位末端标记法（TUNEL）与DNA琼脂糖凝胶电泳观察肾小管上皮细胞凋亡；免疫组化法检测肾组织Bax、Bcl-2的表达。结果:顺铂组大鼠血中BUN、SCr明显高于其它各组，肾脏病理改变明显加重。DNA电泳及TUNEL染色可见大量的肾小管上皮细胞凋亡； MDA含量增加，IHR降低；肾组织Bax表达增加，Bcl-2无明显变化。卡维地洛治疗组大鼠肾功能障碍、肾脏的病理变化减轻； MDA含量下降，IHR增加；肾小管上皮细胞凋亡减少，Bax表达减少，Bcl-2表达增加。结论:肾小管上皮细胞凋亡是顺铂肾毒性的重要原因。卡维地洛可通过减少活性氧族 (ROS)，减少Bax、增加Bcl-2的表达，使Bcl-2/Bax上调，阻止线粒体膜孔(MPT)的开放，抑制肾小管上皮细胞凋亡,减轻顺铂的肾损害。     

LIGHT/TNFSF14减轻顺铂诱导的小鼠急性肾损伤及机制

目的研究与单纯疱疹病毒糖蛋白D竞争结合疱疹病毒侵入介体的淋巴毒素类似物(LIGHT)即肿瘤坏死因子超家族蛋白14(TNFSF14)在顺铂诱导的急性肾损伤(Cis-AKI)中的作用并初步探讨其机制。方法选取雄性野生型(WT)和LIGHT敲除(LIGHT~(-/-))C57BL/6小鼠,分为WT小鼠生理盐水组、 WT小鼠顺铂组、 LIGHT~(-/-)小鼠生理盐水组和LIGHT~(-/-)小鼠顺铂组。其中顺铂组予以单次腹腔注射顺铂(20 mg/kg,200μL),生理盐水组以等体积生理盐水替代。72 h后,处死小鼠,眼球取血,同时收集肾脏组织。全自动生化分析仪检测血尿素氮(BUN)及血清肌酐(Scr)水平; HE染色检测肾组织病理学改变,实时定量PCR检测小鼠肾组织中LIGHT、肾损伤分子1(KIM-1)、白细胞介素6(IL-6)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子α(TNF-α)的mRNA水平;免疫组织化学染色法检测肾组织中LIGHT的表达; Western blot法检测肾组织LIGHT、Bcl2、 BAX、细胞色素C的蛋白水平。结果与生理盐水处理的WT小鼠相比,顺铂处理WT小鼠肾组织LIGHT表达明显升高。与顺铂处理的WT小鼠相比, LIGHT ~(-/-)小鼠顺铂诱导的肾损伤更为严重BUN、 Scr升高和肾脏组织损伤更严重;且肾组织IL-6、 MCP-1和TNF-α的mRNA以及BAX、细胞色素C的蛋白水平增加, Bcl2蛋白水平降低。结论 LIGHT在Cis-AKI中具有保护作用,可能与降低炎症因子分泌及减少细胞凋亡有关。     

苏木酮A对顺铂所致肾损伤中的抗氧化应激作用

目的探讨苏木酮A(sappanone A,SA)能否逆转顺铂(cisplatin,CP)所致肾毒性损害,通过观察肾组织形态及氧化应激指标的变化,探讨其可能的机制,为临床使用SA改善CP所致肾损害的应用提供实验理论依据。方法将Balb/c小鼠(n=8)随机分为5组(Control组、CP组、CP+SA低剂量组、CP+SA中剂量组、CP+SA高剂量组)。全自动生化分析仪测定小鼠血清中BUN和Cr的含量;镜下观察肾脏病理组织学变化及肾间质炎细胞浸润情况;生物化学法检测肾组织中SOD酶活性及MDA含量,TUNEL法检测肾小管凋亡情况。结果 BUN和Cr的含量测定结果显示:与CP组相比,SA干预组小鼠血清中BUN和Cr的含量均显著降低(P0.05),尤其是高剂量SA组效果最明显;HE结合肾损伤评分结果显示:SA干预组小鼠肾小管损伤及肾间质炎细胞浸润程度与CP组相比明显减轻(P0.05);TUNEL结果显示:SA干预组小鼠与CP组相比肾小管细胞凋亡明显减少(P0.05);SA干预组小鼠与CP组相比,肾组织中超氧化物歧化酶活性升高及丙二醛含量明显降低(P0.05),且呈剂量依赖性。结论 SA能够逆转CP所致的肾损伤,可能与改善氧化应激有关。     

减重手术通过激活PPARα抑制氧化应激改善糖尿病大鼠肾功能

目的探讨减重手术对糖尿病大鼠肾损伤的保护作用及其可能的作用机制。方法 SPF级SD大鼠45只,随机分为假手术组(Sham组)、糖尿病肾损伤模型组(DN组)及减重手术干预组(DJB组)。除Sham组外,其余两组大鼠建立糖尿病肾损伤模型,模型成功后DJB组大鼠给予减重手术治疗;生化检测血清肌酐(Scr)和尿素氮(BUN)含量;HE染色观察肾脏组织病理学变化;ELISA检测大鼠肾组织中超过氧化物歧化酶(SOD)与活性及丙二醛(MDA)含量;TUNEL染色观察肾组织细胞凋亡情况;免疫荧光染色检测肾组织过氧化物酶体增殖物激活受体α(PPARα)表达情况;Western blot法检测PI3K/Akt信号通路相关蛋白PI3K、Akt及pAkt的表达。结果经减重手术干预后,与DN组相比,DJB组大鼠Scr、BUN表达明显下降(P0.05),肾脏损伤明显减轻,SOD活性升高而MDA含量降低(P0.05);肾脏细胞凋亡数量降低且PPARα表达增加(P0.05);减重手术干预后,大鼠肾脏组织中PI3K及p-Akt表达明显升高(P0.05)。结论减重手术可以有效减轻糖尿病大鼠肾功能损伤,其作用机制可能与激活PPARα、抑制氧化应激有关。     

N-乙酰半胱氨酸对顺铂导致肾毒性的保护作用及作用机制分析

目的:通过动物实验分析探讨N-乙酰半胱氨酸对于顺铂诱导的肾毒性和肾损伤的保护功能及其机制,为临床药理研究提供参考。方法:选取60只BALB/c小鼠,雌雄各半,喂养7 d后腹腔注射20 mg/kg的顺铂,持续注射3 d诱导并建立急性肾损伤小鼠模型(AKI),后随机分为6组,A组给予5 mg/kg顺铂,B组给予250μg/(100 g·d)的N-乙酰半胱氨酸,C组给予5 mg/kg顺铂+250μg/(100 g·d)的N-乙酰半胱氨酸;D组给予500μg/(100 g·d)的N-乙酰半胱氨酸;E组给予5 mg/kg顺铂+500μg/(100 g·d)的N-乙酰半胱氨酸,F组注射生理盐水做对照,连续治疗7 d后,抽取小鼠眼球血,测定生化指标、炎症因子水平;做肾脏病理切片图评价肾损伤水平,并加以比较。结果:在给药前,6组小鼠的血肌酐(Scr)、尿素氮(BUN)、肾损伤评分(RIS)、肿瘤坏死因子α(TNF-α)、谷胱甘肽(GSH)水平比较差异无统计学意义(P>0.05);给药后,6组上述指标差异有统计学意义(P<0.05):①血清Scr、BUN、TNF-α和肾损伤评分RIS:A组&...     

冬虫夏草菌丝体提取物抑制顺铂诱导的肾小管上皮细胞损伤

目的:探讨冬虫夏草菌丝体(Hirsutella sinensis mycelium,HSM)提取物对顺铂(CDDP)诱导的小鼠肾小管上皮细胞(RTEC)损伤的影响及可能的调控机制。方法:体外实验分5组:正常对照组、顺铂诱导的损伤模型组及低、中、高剂量的HSM干预组。RTEC经HSM预处理2 h后加CDDP刺激,24 h后收取细胞,分别采用Annexin V/PI双染法检测细胞凋亡、Real-time PCR检测凋亡相关基因、炎性因子及模式识别受体的相对表达量。体内实验分3组:对照组、CDDP诱导的小鼠急性肾损伤模型组及HSM治疗组,分别取肾组织进行HE染色及提取RNA和相关基因mRNA水平的检测。结果:HSM预处理可缓解CDDP诱导的凋亡,促进抗凋亡基因Bcl-2的表达,并抑制BAX与Caspase-9;同时降低TNF-α和TLR4的表达。体内实验则显示HSM可有效缓解CDDP诱导的小鼠肾小管损伤。结论:HSM可以降低RTEC凋亡、减轻炎症以改善CDDP诱导的RTEC损伤。     

促红细胞生成素通过调节未折叠蛋白反应减轻顺铂所致的肾小管上皮细胞凋亡

 目的：探讨促红细胞生成素（EPO）能否通过调节未折叠蛋白反应减轻顺铂(CP)诱导的肾小管上皮细胞凋亡。方法：健康雄性SD大鼠随机分为3组（每组12只）,包括正常对照组（control 组）、CP组和CP+重组人EPO组（CP+rHuEPO组）。顺铂或生理盐水注射96 h后处死SD 大鼠,留取血液和肾脏组织,检测血尿素氮（BUN）和血清肌酐（SCr）水平,PAS染色光镜观察肾脏形态结构变化;TUNEL染色检测肾小管上皮细胞凋亡;采用Western blotting法、免疫组化及激光共聚焦技术检测EPO受体(EPOR)和葡萄糖调节蛋白78(GRP78)蛋白表达。结果：与control组比较,CP组与CP+rHuEPO组大鼠BUN及SCr水平均显著升高（P＜0.05）,TUNEL染色显示凋亡细胞阳性率显著上升（P＜0.05）,EPOR及GRP78蛋白表达显著上调（P＜0.05）;PAS染色光镜示CP组肾脏组织结构出现明显损伤性变化;与CP组比较,CP+rHuEPO组SCr水平显著降低（P＜0.05）,凋亡细胞阳性率显著下降（P＜0.05）,EPOR及GRP78蛋白表达下调（P＜0.05）,肾脏病理损伤减轻。结论：EPO可以减轻顺铂引起的肾损害,其机制可能与调节未折叠蛋白反应减轻肾小管上皮细胞凋亡相关。     

人参皂苷Rg1通过TLR4/MyD88/NF-κB p65通路调控小鼠急性肾损伤诱导的急性肝损伤的机制研究

目的：探讨人参皂苷Rg1(GRg1)对小鼠急性肾损伤所诱导的急性肝损伤的保护作用及其调控机制。方法：昆明小鼠随机分为假手术（sham）组、模型（model）组、GRg1组和necrostatin-1 (Nec-1)组，每组10只。制备急性肾损伤模型，24 h后收集血液。采用生化试剂盒检测小鼠血清肌酐（SCr）、血尿素氮（BUN）、天冬氨酸转氨酶（AST）、谷氨酸转氨酶（ALT）、丙二醛（MDA）和超氧化物歧化酶（SOD）水平。采用ELISA法检测炎症因子白细胞介素1β(IL-1β)、IL-6、IL-8和肿瘤坏死因子α(TNF-α)的表达。HE染色观察组织病理学改变，采用免疫组织化学和Western blot法检测TLR4、MyD88和NF-κB p65蛋白的表达水平。结果：与假手术组比较，model组小鼠出现明显的肝细胞坏死、肝肾功能减退，血清中SCr、BUN、AST和ALT均显著升高（P<0.01）,MDA含量显著上升，SOD活性显著降低（P<0.01），且血清中炎症因子IL-1β、IL-6、IL-8和TNF-α含量显著升高（P<0.01）,TLR4、MyD88和N...     

当归多糖治疗小鼠乙醇性肝损伤中丙二醛、超氧化物歧化酶及谷胱甘肽过氧化物酶的变化及意义

目的:探讨当归多糖治疗小鼠乙醇性肝损伤中丙二醛(MDA)、超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSHPx)的变化及意义。方法:通过一次性高浓度乙醇灌胃建立小鼠乙醇性肝损伤模型,之后连续腹腔注射当归多糖6 d,血清生化检测MDA、SOD及GSH-Px,光镜观察肝形态结构变化。结果:小鼠乙醇性肝损伤后,血清MDA显著增高,SOD及GSH-Px显著下降,同时肝组织结构呈弥漫性脂肪变性损伤。用当归多糖治疗后,伴随肝组织结构的修复,血清MDA显著下降,SOD及GSH-Px增高。结论:当归多糖可通过阻断膜脂质过氧化起到保护肝细胞的作用,血清MDA、SOD及GSHPx水平的变化对判断肝的损害程度、病情发展、评估预后有一定的意义。     

Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats

The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.     

Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice

This study investigated the protective effects of pravastatin against cisplatin-induced nephrotoxicity and the possible mechanisms in mice. Pravastatin showed significant protection as evidenced by the decrease of elevated serum creatinine (CRE) and blood urea nitrogen (BUN), and improvement of histopathological injury induced by cisplatin. The formation of kidney malondialdehyde (MDA) with a concomitant reduction of reduced glutathione (GSH) were inhibited by pravastatin, while the activities of kidney superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) were increased. The over expressions of kidney induced nitric oxide synthase (iNOS) and nitrotyrosine (3-NT) were suppressed by pravastatin. Pravastatin suppressed cisplatin-induced p38 mitogen-activated protein kinase (MAPK) activation in the kidney of mice. These results suggest that pravastatin pre-administration can prevent the nephrotoxicity induced by cisplatin. Pravastatin may exert the protective effect via inhibiting oxidative and nitrosative stress.     

己酮可可碱对抗兔肾脏缺血再灌注损伤的实验研究

目的: 研究己酮可可碱对抗兔肾脏缺血再灌注损伤作用。方法: 新西兰兔50只,随机分成5组:假手术组、缺血再灌注组(I/R)、I/R+己酮可可碱组、I/R+低温组、I/R+己酮可可碱+低温组。除假手术组外,其余4组均用动脉夹夹闭左侧肾动脉60min后恢复血流灌注,24h后取左肾分别检测肾组织匀浆的SOD、MDA和BUN、SCr水平的变化,并作病理观察。结果: I/R组肾小管出现水样变性、出血坏死,出血坏死组织中大量炎性细胞浸润,近曲小管上皮细胞线粒体高度肿胀,嵴极其紊乱、模糊、甚至消失;I/R+己酮可可碱组和I/R+低温组损伤减轻;I/R+己酮可可碱+低温组和假手术组形态正常。再灌注24h后I/R组BUN、SCr、MDA水平明显高于其它各组(P＜0.05),SOD活性明显低于其它各组(P＜0.05),I/R+低温组和I/R+己酮可可碱组BUN、SCr、MDA水平明显低于I/R组(P＜0.05),SOD活性明显高于I/R(P＜0.05),低温+己酮可可碱组的上述指标与假手术组无显著差异(P>0.05)。结论: 己酮可可碱有对抗兔肾脏缺血再灌注损伤的作用。     

辛伐他汀对大鼠肾缺血再灌注损伤后心肌Bcl-2和Bax蛋白表达的影响

目的:观察辛伐他汀对肾缺血再灌注损伤后心肌组织的影响及其机制。方法:随机将36只大鼠分为假手术组、肾缺血再灌注组和辛伐他汀组,每组12只。后2组用夹闭双侧肾动脉的方法复制肾缺血再灌注损伤模型;辛伐他汀组在造模前给予辛伐他汀(20 mg·kg~(-1)·d~(-1))灌胃,持续2周。用生化检查检测血清肌酐(SCr)、血尿素氮(BUN)、心肌组织丙二醛(MDA)含量及乳酸脱氢酶(LDH)、肌酸激酶(CK)和超氧化物歧化酶(SOD)的活性,并用Western blot法检测Bcl-2和Bax的表达水平。结果:与假手术组比,缺血再灌注组SCr、BUN和心肌MDA含量均升高(P0.05),心肌LDH和CK活性增强(P0.05),心肌SOD活性明显下降(P0.05);与缺血再灌注组比较,辛伐他汀组SCr、BUN和心肌MDA的含量降低(P0.05),心肌LDH和CK活性明显减弱(P0.05),而心肌SOD活性增强(P0.05)。与假手术组比较,心肌Bcl-2与Bax的蛋白表达水平在肾缺血再灌注组增多(P0.05);与缺血组相比,Bax表达在辛伐他汀组明显降低,而Bcl-2表达增加(P0.05)。结论:辛伐他汀对肾缺血再灌注后的心肌有保护作用,保护机制可能与辛伐他汀可以消除自由基、升高Bcl-2蛋白表达和降低Bax蛋白表达有一定关系。     

芝麻素改善自发性高血压大鼠肾损伤的作用及与PI3K/AKT/mTOR信号通路的关系

 目的: 观察芝麻素对自发性高血压大鼠(spontaneously hypertensive rats,SHR)肾脏损伤的作用及与PI3K/AKT/mTOR信号通路之间的关系。方法: 雄性SHR随机分成模型组、芝麻素低剂量(80 mg/kg)、高剂量(160 mg/kg)组及卡托普利(30 mg/kg)组。同时选取同周龄WKY大鼠作为正常对照组。每日灌胃1次,模型组、正常对照组给予0.5%羧甲基纤维素钠(CMC-Na),给药组给予CMC-Na溶解的上述剂量药物,给药前及给药后每隔2周测量1次血压。12周后,检测血尿素氮(BUN)、肌酐(SCr)及尿微量白蛋白(U-mAlb)含量;测定肾脏丙二醛(MDA)和超氧化物歧化酶(SOD)水平;HE、Masson染色观察肾组织病理学变化;TUNEL法检测肾组织细胞凋亡率;Western blot法检测肾脏p-AKT、p-mTOR、4EBP1、S6K1、Bcl-2和Bax的蛋白水平。结果: 芝麻素能降低SHR舒张压,明显改善肾组织的病理学变化,降低肾脏BUN、SCr、U-mAlb、MDA含量及细胞凋亡率,提高SOD活性,显著减少p-AKT、p-mTOR、4EBP1、S6K1和Bax的蛋白水平,增加Bcl-2的蛋白表达。结论: 芝麻素减轻SHR大鼠肾脏损伤的作用机制可能与降低血压、对抗氧化应激、抑制细胞凋亡、阻滞过度活化的PI3K/AKT/mTOR信号通路有关。     

Involvement of oxidative stress in the mechanism of triptolide-induced acute nephrotoxicity in rats

Triptolide is one of the most widely used and one of the most potent Chinese traditional herbal medicines. However, side effects, especially nephrotoxicity, limit the use of triptolide. It has been reported that oxidative stress is involved in drug-induced nephrotoxicity. In the present study, we focused on observing triptolide-induced acute nephrotoxicity in rats and investigating whether or not oxidative stress is involved in the pathogenesis of this process. The results showed that a single large dose peritoneal injection of triptolide caused severe oxidative stress characterized by significant decreases of renal SOD and GSH-Px activities, as well as significant increase of renal MDA content and also led to severe impairment of renal structure and function characterized by injury of renal tubules observed in HE-stained and TUNEL-stained slides and increases of Cre and BUN concentrations in a short time. However, pretreatment with the antioxidant vitamin C significantly ameliorated triptolide-induced depletion in renal SOD and GSH-Px activities, caused marked normalization of renal MDA content and also blunt the impairment of renal tubules and renal function. These results suggest that triptolide induces oxidative stress via impairing the antioxidant system, and oxidative stress contributes, at least in part, to the mechanism of triptolide-induced acute nephrotoxicity.     

肌肽对糖尿病肾病大鼠氧化应激及NF-κB信号通路的影响

目的　探讨肌肽对糖尿病肾病（DN）大鼠肾组织的保护作用及其对氧化应激、NF-κB信号通路的影响。 方法　60只SPF级8周龄雄性SD大鼠，随机选取12只为对照组，其余予以高糖高脂饮食+链脲佐菌素腹腔注射建立糖尿病模型。注射链脲佐菌素3 d后，将符合糖尿病标准大鼠随机分为模型组、肌肽（100、300、900 mg/kg）组。肌肽各组分别灌胃100、300、900 mg/kg肌肽，每日1次。8周后，检测空腹血糖（FBG）、血清肌酐（Scr）、尿素氮（BUN）、24 h尿微量白蛋白（mAlb）。PAS染色法观察大鼠肾形态学变化；试剂盒检测肾组织的超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-Px）含量；免疫组织化学及Western blot检测肾组织P-NF-κB P65蛋白的表达。 结果　 DN大鼠建模成功。与模型组相比，肌肽组肾组织病理损伤明显减轻。肌肽各组大鼠mAlb、FBG、BUN水平下降，呈量-效依赖性关系（P<0.05），而SOD、GSH、GSH-Px的含量逐级升高，同时MDA和P-NF-κB P65含量减少。 结论　肌肽对DN模型大鼠肾组织具有保护作用，其机制可能与抑制氧化应激和NF-κB信号通路异常激活有关。     

Panax notoginseng saponins attenuates cisplatin-induced nephrotoxicity via inhibiting the mitochondrial pathway of apoptosis

The goal of this experiment was to investigate the protective effect and the molecular mechanism of Panax Notoginseng Saponins (PNS) on cisplatin-induced nephrotoxicity through mitochondrial pathway of apoptosis. The rats underwent intraperitoneal injection with a single dose of cisplatin, a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day for 8 days. At day 1, 4 and 8 after exposure to cisplatin, the concentrations of blood urea nitrogen (BUN), serum creatinine (Scr) and urinary N-acetyl-β-D-Glucosaminidase (NAG) were determined using commercial kits. The pathological change of renal tissue were examined using H & E staining and transmission electron microscopy. The rate of apoptosis and the expression of Bcl-2 in rat renal tissue were detected by using TUNEL staining and Western bloting, respectively. And the expressions of Bax and caspases 9 were detected by immunnohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by the decrease in concentration of blood BUN, Scr and urinary NAG, as well as the attenuation of renal histopathological damage. Furthermore, PNS reduced the rate of apoptosis, and the mechanism studies showed that PNS inhibited the expression of Bax and caspase 9, while increased the expression of Bcl-2. This study first demonstrated that PNS can protect against cisplatin-induced nephrotoxicity and reduce renal tissue apoptosis via inhibiting the mitochondrial pathway.     

Protective effect of Salvia Miltiorrhizae injection on N(G)-nitro-d-arginine induced nitric oxide deficient and oxidative damage in rat kidney

N(G)-nitro-d-arginine (d-NNA) could convert into N(G)-nitro-l-arginine (l-NNA) in vivo, and kidney is the major target organ. In the chiral inversion process, a number of reactive oxygen species (ROS) were generated and NOS activity was inhibited, which may cause renal damage. Salvia miltiorrhiza (SM), a traditional Chinese drug, was used in the treatment of cardiovascular diseases and chronic renal failure. The aim of the present study was to investigate the kidney damage caused by d-NNA administration for 12 weeks and to evaluate the effects of treatment with SM on d-NNA-induced kidney damage. The rats, induced with d-NNA for period of 12 weeks, showed significant elevation of Blood Urea Nitrogen (BUN), Creatinine (Crea) and MDA levels, and significant decrease of SOD and GSH-Px activities, as compared with control group. In addition, the kidney of rats induced with d-NNA only showed remarkable histopathology, including severe mononuclear cell infiltration, mild tubular dilatation and congestion, and moderate interstitial desmoplasia. After 4 weeks SM treatment, the activity of SOD, GSH-Px and iNOS and the production of NO were significantly higher (P < 0.05), and the levels of BUN, Crea and MDA were significantly lower than that of d-NNA only group (P < 0.05). In addition, treatment with SM showed histopathological protection in tubular dilatation, congestion, mononuclear cell infiltration and interstitial desmoplasia. The present results indicate that the toxicity of d-NNA relates to its ability to generate oxidative stress and upregulate NOS activity in rat kidney. SM probably ameliorates d-NNA-induced nephrotoxicity in rats according to scavenging free radical and upregulating NOS activity.     

不同剂量补肾方药对顺铂所致大鼠肾毒性的影响

目的：观察不同剂量中药对顺铂(DDP)所致大鼠肾毒性的影响。方法：经尾静脉注射DDP诱发大鼠肾毒性,同时给大鼠灌服不同剂量益气补肾中药,观察大鼠肾组织在光镜及电镜下形态的改变,并检测大鼠血清尿素氮(BUN)的含量。结果：中剂量益气补肾中药能明显减轻DDP所致大鼠的肾损害,并使BUN含量明显降低。结论：适当剂量的益气补肾中药是拮抗DDP引起的肾毒性的有效药物。