中医药抗顺铂肾毒性的研究进展

顺铂（DDP）是一种有效的临床抗肿瘤药物,其疗效与用药剂量成正比,但其严重肾毒性是临床应用受限的主要因素。近年国内许多中医学者在顺铂肾毒性的防治方面进行了临床与实验研究,可为临床更好地运用顺铂提供参考。     

茶多酚对顺铂所致肾损伤保护作用的实验研究

顺铂 (ＤＤＰ)已广泛应用于临床 ,并显示了较强的抗癌作用 ,但是顺铂也具有重金属类物质的毒性作用 ,其中最主要的是对肾脏的毒性作用。在临床应用中 ,往往由于严重的肾功能损伤而限制了药物的使用。茶多酚 (ＴＰ)是从茶叶中提取的一种酚类物质[1 ] ,具有抗癌、防癌、增强机体免疫力、清除自由基、阻止脂质过氧化等功能。我们拟探讨ＴＰ对顺铂所致机体损伤的保护作用 ,以期为临床顺铂的毒性防护提供新思路。1　材料与方法1 1　材料　昆明种小鼠 ,体重为 18～ 2 2ｇ ,由华北煤炭医学院动物中心提供 ;药品及试剂 :ＤＤＰ、ＴＰ、硫代硫酸钠 (…     

肾损伤分子1对顺铂诱导的大鼠急性肾损伤的预测研究

目的 对肾损伤分子1 (KIM-1)预测顺铂诱导的大鼠急性肾损伤进行研究.方法 以顺铂为工具药,诱导大鼠急性肾损伤模型.采集尿样、肾组织样本,对肾组织样本进行病理切片检查,以确定造模是否成功.用ELISA法测定尿样中KIM-1蛋白含量;RT-PCR法检测大鼠肾脏KIM-1基因表达水平;Western blotting法检测大鼠肾组织中KIM-1的蛋白含量,并通过免疫组化法定性定位分析大鼠肾组织中KIM-1蛋白表达情况,以确定急性肾损伤发生时KIM-1是否可以作为敏感的检测指标.结果 当模型组大鼠肾脏皮髓交界处出现程度不等的肾小管扩张,肾小管上皮细胞变性、坏死脱落,基底膜裸露等病理改变时,ELISA法检测尿KIM-1,RT-PCR法和Western blotting法检测肾组织中的KIM-1表达水平均明显升高,免疫组化显示模型组所有大鼠在肾皮髓交界部位可见大量的染色阳性的肾小管,该染色阳性区域与组织病理学检查中的异常肾小管分布区域基本一致.结论 KIM-1可作为一种敏感的生物标志物对顺铂诱导的大鼠急性肾损伤进行预测.     

左旋肉碱改善顺铂诱导肾损伤机制的相关研究

左旋肉碱可有效改善某些药物引起的肾损伤,其在顺铂诱导的急性肾损伤中起保护作用。多数研究认为左旋肉碱主要通过抗氧化、抗炎及抗凋亡作用发挥对顺铂肾毒性的保护作用,但目前发现其机制还涉及其他方面。该文就左旋肉碱改善顺铂肾损伤的相关研究综述如下。     

人参茎叶总皂苷对顺铂致小鼠肾损伤的保护作用及机制

目的观察人参茎叶总皂苷(GSLS)对顺铂(CDDP)诱导肾损伤小鼠的保护作用,并探讨其可能机制。方法 32只雄性ICR小鼠随机分为正常对照组、CDDP模型组(一次性ip给予CDDP 20 mg·kg~(-1)诱导小鼠肾损伤)、CDDP+GSLS 150和300 mg·kg~(-1)给药组。给药组连续给予GSLS 7 d,末次给药1 h后,一次性ip给予CDDP 20 mg·kg~(-1)诱导小鼠肾损伤,继续给予GSLS 150和300 mg·kg~(-1)3 d,分别采用脲酶法和肌氨酸氧化酶法检测小鼠血尿素氮(BUN)和肌酐(CRE)水平,评价肾功能的变化;分别采用可见光法和微量酶标法检测肾组织中过氧化氢酶(CAT)和还原型谷胱甘肽(GSH)水平,评价小鼠肾组织中氧化应激的水平;采用生物素双抗体夹心酶联免疫吸附法检测肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β),评价肾组织中炎症水平;HE和PAS染色法观察肾组织病理变化;TUNEL和Hoechst33258染色法观察细胞凋亡。结果与正常对照组比较,CDDP组小鼠体质量显著下降(P<0.05),肾指数和血清中CRE,BUN,TNF-α和IL-1β水平显著升高(P<0.05,P<0.01),其中CRE和BUN分别升高了1倍和3倍,肾组织CAT和GSH显著下降(P<0.05);CDDP组肾组织中出现肾小球肿胀、肾小管扩张、肾小球上皮细胞坏死,管腔内出现透明管型,细胞核固缩或消失,肾间质水肿和炎症细胞浸润,大量糖原沉积,此外还有大量的TUNEL阳性细胞和Hoechst33258阳性细胞表达;与CDDP组比较,GSLS各治疗组小鼠血清中CRE和BUN水平明显降低(P<0.05,P<0.01),肾组织糖原沉积减少,肾小管上皮细胞凋亡减少(P<0.05);CDDP+GSLS 300 mg·kg~(-1)组TNF-α和IL-1β显著降低(P<0.05),CAT和GSH显著升高(P<0.05),肾组织坏死程度减轻(P<0.05)。结论GSLS对CDDP诱导的小鼠肾损伤具有保护作用,其机制可能与改善氧化应激、减少炎症反应及抗细胞凋亡有关。     

促红细胞生成素对顺铂急性肾损伤的保护作用

目的：探讨促红细胞生成索（Erythopoietin,Epo）对顺铂（CDDP）急性肾损伤的保护作用及机制。方法：建立大鼠CDDP急性肾损伤动物模型,将SD大鼠随机分为生理盐水（NS）组、CDDP组及Epo治疗（CDDP＋Epo治疗）,观察各组血清尿素氮（BUN）、血肌酐（Scr）和肾组织匀浆超氧化物歧化酶（SOD）、丙二醛（MDA）及肿瘤坏死因子-α（TNF—α）的变化。结果：Epo治疗组血清BUN、Scr及MDA、TNF-α较CDDP组显著下降（P〈0．05）,SOD显著升高（P〈0．05）。结论：Epo可提高SOD,降低TNF—α对CDDP急性肾损伤具有保护作用。     

黄芪对顺铂耳蜗毒性防护作用的实验研究

目的探讨黄芪对顺铂耳蜗毒性所起防护作用。方法将豚鼠随机分成对照组,顺铂组,黄芪组。测试听性脑干反应（ABR）阈值和I波潜伏期及光镜观察。结果ABR阈值黄芪组较顺铂组明显降低及I波潜伏期缩短（P〈0．01）。黄芪组耳蜗底回螺旋器内外毛细胞排列较整齐,结构基本正常。结论黄芪可减轻顺铂耳蜗毒性。     

茶多酚对顺铂所致肾损伤保护作用的实验研究

目的　 研究茶多酚 (TP)对顺铂 (DDP)所致肾毒性的保护作用及其机制。 方法 　将小鼠随机分为 4组 :对照组、DDP组、DDP +低剂量TP组、DDP +高剂量TP组 ,分别腹腔注射生理盐水、顺铂 2mg/kg ,喂饲TP0 5g/kg ,1 0g/kg ,测定血清中尿素氮 (BUN)、肌酐 (Cr)和肾组织匀浆中超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH Px)活性及丙二醛 (MDA)含量 ,观察肾脏病理结构的变化。 结果 　DDP组小鼠血清中BUN及Cr值升高 ,与对照组比较差异有极显著意义 (P <0 0 1) ,加入高剂量TP后 ,BUN及Cr值明显低于DDP组 (P <0 0 5 )。给予DDP后 ,肾组织中SOD、GSH Px活性降低 ,MDA含量升高 ,与对照组比较 ,差异有显著性 (P <0 0 5 ,P <0 0 1)。喂饲TP后SOD、GSH Px值有所上升 ,MDA下降 ,DDP +低剂量TP组与DDP组比较 ,SOD、MDA两项指标差异有显著性 (P <0 0 5 ) ,但与对照组比较 ,3项指标均存在显著差异 (P <0 0 5 ) ;DDP +高剂量TP组SOD、GSH Px值升高 ,MDA含量降低较明显 ,与DDP组比较差异有显著性 (P <0 0 5 ,P <0 0 1)。光镜下肾组织超微结构亦见改善。 结论 　TP在一定程度上可缓解DDP所致的肾损伤 ,其机制可能与抗氧化功能有关。     

贝那普利防治顺铂肾损伤的实验研究

目的探讨贝那普利防治顺铂肾损伤的作用及其机制。方法取36只大鼠,随机分为正常组、模型组、贝那普利组,各12只。采用顺铂尾静脉注射复制顺铂肾损伤模型。6周后,观察各组大鼠肾组织的病理改变及24 h尿蛋白、血肌酐、血尿素氮、肾脏血管紧张素Ⅱ（AngⅡ）水平。结果与模型组比较,贝那普利组大鼠血肌酐、血清尿素氮的含量明显降低（P〈0.05）,肾脏的病理变化明显减轻,肾组织AngⅡ含量下降（P〈0.01）。结论贝那普利可通过降低AngⅡ含量来改善肾功能,减轻肾损伤。     

维生素C对顺铂所致大鼠肾损伤的保护作用

目的研究维生素C（Vit C）对顺铂所致肾损伤的保护作用,并探讨其可能的机制。方法将40只成年雌性SD大鼠按体重分成5组,分别为正常对照组（A组,生理盐水）、Vit C对照组（B组,500mg／kg）、顺铂化疗模型组（C组,6mg／kg）、顺铂（6mg／kg）＋Vit C（50mg／kg或500mg／kg）干预组（D1组及D2组）。腹腔注射Vit C进行前、中、后期全程保护,并于顺铂给药5d后采血处死动物,测定血清尿素氮（BUN）、肌酐（Cr）、肾皮质匀浆丙二醛（MDA）含量及谷胱甘肽过氧化物酶（GSH—Px）、超氧化物歧化酶（SOD）活力的变化。结果与C组相比,D1组及D2组的血清Cr及BUN、肾皮质匀浆MDA含量明显下降（P〈0．01或P〈0．05）,GSH—Px和SOD活力略有增加。结论Vit C可以减轻顺铂所致肾损伤,作用机制可能与其抗氧化作用和清除自由基活性密切相关。     

黄芪防护高剂量顺铂所致肾毒性的动物实验

目的：探讨不同剂量的中药黄芪对顺铂所致肾毒性的防护作用,以期指导临床改变目前高剂量顺铂必须水化的现状。方法：以７ ｍｇ·ｋｇ－１ 顺铂单次腹腔注射建立小鼠的肾损模型,于实验的第１～７ 天分别给予不同剂量的黄芪腹腔注射。评估小鼠血尿素氮、血肌酐、血ＮＡＧ酶及肾脏病理学改变。同样的方法实验Ｓ１８０ 荷瘤小鼠并评估瘤重。结果：不同剂量的黄芪均能明显改善顺铂所致小鼠血尿素氮、血肌酐、血ＮＡＧ酶的增高,并与黄芪的剂量正相关。但当黄芪剂量增加到一定数值,其保护作用稳定,对顺铂的抗肿瘤活性均无影响。获病理学支持。结论：黄芪确能防护顺铂所致的肾毒性且不影响其抗瘤活性     

人参皂甙对顺铂所致大鼠肾损害的保护作用

通过药物与肾皮质薄片直接孵育法和注射给药法观察了人参皂甙（Ｇｉｎ）对顺铂（ＣＰ）所致大鼠肾损害的作用。结果表明：ＣＰ１．０ｍｍｏｌ·Ｌ￣（－１）在含有对氨基马尿酸（ＰＡＨ）的生理盐水溶液中与肾薄片孵育１２０ｍｉｎ，导致薄片中ＰＡＨ的蓄积明显减少，Ｇｉｎ８０ｍｇ·Ｌ￣（－１）增加ＰＡＨ的蓄积并抑制ＣＰ引起的ＰＡＨ蓄积减少。ＣＰ７．５ｍｇ·ｋｇ￣（－１）ｉｐ导致时间依赖性的血浆尿素氮（ＢＵＮ）升高，肾皮质组织中超氧化物歧化酶（ＳＯＤ）活性降低和脂质过氧化代谢产物丙二醛（ＭＤＡ）升高Ｇｉｎ５０ｍｇ·ｋｇ￣（－１）每日２次ｉｐ抑制ＣＰ所致的ＢＵＮ和ＭＤＡ升高及ＳＯＤ活性降低，推测Ｇｉｎ对ＣＰ所致大鼠肾损害的保护作用可能与其增强肾小管细胞的内在反应性和抗脂质过氧化作用有关。     

药源性肾损害的诊断与治疗探讨

目的:探讨药源性肾损害的治疗,促进合理使用药物.方法:总结我院对药源性肾损害的临床诊断及治疗,停用对肾损害的可疑药物,对症治疗.结果:药源性肾损害的患者基本痊愈或好转.结论:临床应严格掌握用药指征,密切观察用药后反应,尽可能避免或减少药源性肾损害的发生.     

Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice

Acetaminophen, a widely used analgesic and antipyretic, is known to cause hepatic and renal injury in humans and experimental animals when administered in high doses. It was reported that these toxic effects of acetaminophen are due to oxidative reactions that take place during its metabolism. In this study we aimed to investigate the possible beneficial effect of 2-mercaptoethane sulphonate (MESNA), an antioxidant agent, against acetaminophen toxicity in mice. Balb-c mice were injected i.p. with: vehicle (the control group); a single dose of 150 mg kg(-1) MESNA (MES group); a single dose of 900 mg kg(-1) i.p. acetaminophen (AA4h and AA24h groups); and MESNA, at a dose of 150 mg kg(-1) after acetaminophen injection (AA4h-MES and AA24h-MES groups). The MESNA injection was repeated once more 12 h after the first injection in the AA24h-MES group. Blood urea nitrogen, serum creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in blood and glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver and kidney tissues were measured. Tissues also were examined microscopically. Blood urea nitrogen and serum creatinine, which were increased significantly (P < 0.001) following acetaminophen treatment were decreased significantly (P < 0.05-0.001) after treatment with MESNA. The ALT and AST levels were also increased significantly (P < 0.001) after acetaminophen treatment but were not reduced with MESNA. Acetaminophen treatment caused a significant (P < 0.05-0.001) decrease in GSH levels whereas MDA levels and MPO activity were increased in both tissues. These changes were reversed by MESNA treatment. Collagen contents of the liver and kidney tissues were increased by acetaminophen treatment (P < 0.001) and reversed back to the control levels with MESNA. Our results imply that acetaminophen causes oxidative damage in hepatic and renal tissues and that MESNA, via its antioxidant effects, protects these tissues. Therefore, its therapeutic role as a 'tissue injury-limiting agent' must be elucidated further in drug-induced oxidative damage.     

小剂量肠溶阿司匹林致肾损害16例分析

目的:探讨小剂量肠溶阿司匹林致肾损害问题。方法:对本院1995年1月-2003年8月收治的服用小剂量肠溶阿司匹林患者600例进行回顾性调查分析。结果:600例服用小剂量肠溶阿司匹林(50～75mg·d-1)的患者中,16例发生肾损害,并且剂量越大,疗程越长,肾损害发生数越多。在发现后及时停用阿司匹林,全部病例肾功能均逐渐恢复正常。结论:本组资料显示,小剂量长期服用也可致肾损害。对长期服用阿司匹林的患者,尤其是老年人应定期检查尿常规、肾功能。     

Ramipril对顺铂和肾缺血再灌所致大鼠肾损害的保护

顺铂ｉｐ或体外直接与肾薄片孵育，均可导致大鼠肾皮质中ＡＴＰ浓度降低，对氨基马尿酸蓄积减少，丙二醛和血尿素氮升高。大鼠肾动脉结扎１ｈ，放开灌流３ｈ，诱发了类似的肾损害。血管紧张素转化酶抑制剂ＲａｍｉＰｒｉｌｉＰ给予接受顺铂处理或接受肾动脉结扎的大鼠，或加入到含顺铂的孵育液中，均能明显抑制顺铂和肾缺血再灌注诱发的ＡＴＰ减少，血尿素氮和丙二醛升高，但对对氨基马尿酸蓄积的减少无保护作用。ＲａｍｉＰｒｉｌ对上述肾损害的保护作用机制可能与其抗脂质过氧化作用有关。     

Nephroprotective efficacy of chrysin against cisplatin-induced toxicity via attenuation of oxidative stress

Objectives Cisplatin‐induced nephrotoxicity is the main cause for its dose‐limited use in the treatment of various cancers and results in acute renal cell injury through generation of reactive oxygen species. Chrysin possess antioxidant, anti‐inflammatory and anti‐cancer properties. The aim of this study was to investigate the protective efficacy of chrysin against cisplatin‐induced nephrotoxicity. Methods Thirty male Wistar rats were divided into five groups with six rats in each group. Group I served as control and received corn oil (vehicle of chrysin) for 14 days and 0.9% saline (vehicle of cisplatin) on day 14 only. Group II received a single intraperitoneal injection of cisplatin on day 14. Group III and IV were pretreated with two different doses of chrysin in addition to cisplatin and group V received chrysin only. Rats were examined for the effect of chrysin on cisplatin induced depletion of antioxidant enzymes, induction of lipid peroxidation and DNA damage in the kidney, utilizing a well‐established model of cisplatin‐induced nephropathy. Key findings Pretreatment with chrysin significantly attenuated cisplatin‐induced renal oxidative damage by diminishing the DNA damage and toxicity markers, such as creatinine and blood urea nitrogen, lipid peroxidation and xanthine oxidase activity, accompanied by increase in enzymatic (catalase, glutathione peroxidase, glutathione reductase and glutathione‐S‐transferase) and non‐enzymatic (reduced glutathione) antioxidant status. Histological findings further substantiated the protective efficacy of chrysin, which reduced cisplatin‐induced renal damage. Conclusions The data of the present study suggest that chrysin effectively suppress cisplatin‐induced renal injury by ameliorating oxidative stress.     

高血压对心脏损害和治疗对策

目的探讨高血压与心脏损害的关系,观察比索洛尔治疗高血压性心脏病的疗效。方法随机选择高血压心脏病患者84例采用比索洛尔治疗。观察服用1年后观察服药前、后及作血压和超声心动图检查。结果观察降低血压、改善左室舒张功能与治疗前比较差异有统计意义（P〈0.05）。改善心功能效率明显,治疗前后比较差异有统计学意义（P〈0.05）。结论比索洛尔治疗高血压、改善心功能有效安全。     

脑出血并发急性肾功能损害的原因分析

研究脑出血并发急性肾功能损害病人病死率及其发生原因。方法收集１９６例脑出血病人,其中９２例并发急性肾功能损害者作为Ａ组,与１０４例无肾损害者作为Ｂ组进行对照组。结果Ａ组死亡３６例,病死率３９．１％;Ｂ组死亡８例,病死率７．６９％,二者差异有显著意义（ｘ＾２＝２７．５６５,Ｐ〈０．０１）具有糖尿病病史者百分比,Ａ组明显高于Ｂ组。兵脑出血发生率,Ａ组明显高于Ｂ组（０．０５〉Ｐ〉０．０１）。出血量,Ａ组     

Protective effect of Gymnema montanum against renal damage in experimental diabetic rats

Gymnema montanum Hook (Asclepiadaceae), is an endemic plant species of India, traditionally used for diabetes and its management. In this experiment, the ethanol extract of G. montanum (GLEt) at a dose of 200 mg/kg body weight was tested to evaluate its effect on renal damage in alloxan-induced diabetic rats and the efficacy was compared with standard hypoglycemic drug, glibenclamide (600 μg/kg body weight). The GLEt and glibenclamide were administered orally for 3 weeks and the effects on glucose, insulin, renal markers including urea, creatinine and uric acid, lipid peroxidation markers including thiobarbituric reactive substances (TBARS) and hydroperoxides and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities in kidney were studied. In addition, the urinary protein profile was studied using SDS–PAGE. The results indicated that the GLEt significantly normalized the elevated blood glucose, renal markers and lipid peroxidation markers and increased antioxidant levels in diabetic kidney. The diabetic rats excreted large amount of proteins than untreated rats which was normalized during the treatment with GLEt. In conclusion, the GLEt was found to be more effective in reducing oxidative stress, thus confirming the ethnopharmacological use of G. montanum in protecting diabetes and its complications.