番茄红素对顺铂所致大鼠脏器损伤的保护效果评价

Evaluation of the Protective Effect of Lycopene on Organ Injury Induced by Cisplatin in Rats

[目的]评价不同浓度番茄红素(lycopene,LCP)对顺铂(CDDP)诱导大鼠脏器损伤的保护效果。[方法]将30只雄性Wistar大鼠随机分为5组(n=6),分别为对照组(CON)、CDDP组及不同浓度LCP处理组(5 mg/kg,LLCP组;10 mg/kg,MLCP组;50 mg/kg,HLCP组)。CON和CDDP组大鼠每天灌胃1 mL/kg玉米油,LLCP、MLCP和HLCP组大鼠每天灌胃相应浓度的LCP,连续灌胃28 d。除CON组外,其余各组在第26天单次腹腔注射CDDP(7 mg/kg)。试验结束后采集大鼠胃、小肠(十二指肠、空肠和回肠)、肝脏、肾脏组织及血液样本。通过生理和生化指标检测、HE染色、ELISA和Western blotting方法评价不同浓度LCP在CDDP所致大鼠急性损伤中的保护作用。[结果]与CON组相比,CDDP组大鼠体重、采食量和饮水量均极显著或显著下降(P<0.01;P<0.05),血清中谷草转氨酶(AST)、尿素氮(BUN)、肌酐(CRE)等6项生化指标水平、丙二醛(MDA)、白细胞介素-8(IL-8)、IL-6、肿瘤坏死因子-α(TNF-α)含量均显著或极显著升高(P<0.05;P<0.01),超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性极显著下降(P<0.01),大鼠胃、小肠、肝脏和肾脏组织病理学损伤严重。与CDDP组相比,MLCP组大鼠体重、采食量和饮水量均显著升高(P<0.05),血清中AST、ALT等6项生化指标水平以及MDA、IL-8、TNF-α和IL-6含量均显著降低(P<0.05),脏器组织病理学损伤减轻。Western blotting结果显示,与CON组相比,CDDP组大鼠不同组织中TNF-α和IL-6蛋白表达量均极显著升高(P<0.01),IL-10蛋白表达量极显著下降(P<0.01)。与CDDP组相比,MLCP组大鼠各组织中TNF-α和IL-6蛋白表达量均极显著或显著降低(P<0.01;P<0.05),IL-10蛋白表达量均显著或极显著升高(P<0.01;P<0.05)。[结论]LCP能通过抑制氧化应激和炎症反应改善CDDP诱导的大鼠胃、小肠、肝脏和肾脏损伤,本试验条件下10 mg/kg LCP作用效果最佳。

[Objective]The aim of this study was to evaluate the protective effect of lycopene(LCP)on organ injury induced by cisplatin(CDDP)in rats.[Method]Thirty male Wistar rats were randomly divided into 5 groups(n=6),which were control group(CON),CDDP and different LCP treatment groups(5 mg/kg,LLCP group;10 mg/kg,MLCP group;50 mg/kg,HLCP group).Rats in CON and CDDP groups were given 1 mL/kg corn oil per day,and rats in LLCP,MLCP and HLCP groups were given the corresponding concentration of LCP per day,and consecutive for 28 days.Except CON group,the other groups were given a single intraperitoneal injection of CDDP(7 mg/kg)on day 26.After the experiment,samples of stomach,small intestine(duodenum,jejunum and ileum),liver,kidney and blood were collected.The protective effects of different concentrations of LCP on CDDP-induced acute injury in rats were evaluated by physiological and biochemical indexes detection,HE staining,ELISA and Western blotting.[Result]Compared with CON group,body weight,feed intake and water intake of rats in CDDP group were extremely significantly or significantly decreased(P<0.01 or P<0.05).Serum levels of aspartate aminotransferase(AST),urea nitrogen(BUN),creatinine(CRE)and malondialdehyde(MDA),interleukin-8(IL-8),IL-6 and tumor necrosis factor-α(TNF-α)were significantly or extremely significantly increased(P<0.05 or P<0.01).The activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were extremely significantly decreased(P<0.01),and the histopathological injuries of stomach,small intestine,liver and kidney were serious.Compared with CDDP group,the body weight,feed intake and water intake of rats in MLCP group were significantly increased(P<0.05),the levels of 6 biochemical indexes such as AST and ALT and the contents of MDA,IL-8,TNF-αand IL-6 in serum were significantly decreased(P<0.05),and the organ histomathological damage was alleviated.Western blotting results showed that compared with CON group,the expression of TNF-αand IL-6 proteins in different tissues of rats in CDDP group were extremely significantly increased(P<0.01),while the expression of IL-10 protein was extremely significantly decreased(P<0.01).Compared with CDDP group,the expression of TNF-αand IL-6 proteins in all tissues of MLCP group were extremely significantly or significantly decreased(P<0.01 or P<0.05),the expression of IL-10 protein was extremely significantly or significantly increased(P<0.01 or P<0.05).[Conclusion]LCP could improve the stomach,small intestine,liver and kidney injury in CDDP-induced rats by inhibiting oxidative stress and inflammation.Under this experiment conditions,10 mg/kg LCP had the best effect.