麻黄水提物对顺铂所致大鼠肾损伤的影响
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摘要
目的:研究麻黄水提物对顺铂所致大鼠肾损伤的作用。方法:将大鼠随机分成5组:空白组、模型组、麻黄水提物高(400 mg·kg~(-1))、中(200 mg·kg~(-1))、低(100 mg·kg~(-1))剂量组,每组8只。空白组和模型组每日灌胃给予生理盐水(1 ml/100g),给药组分别每日灌胃给予麻黄水提物,连续10 d,并在第6天早晨分别腹腔给予模型组和麻黄水提物组顺铂(8 mg·kg~(-1))造成大鼠肾损伤。观察大鼠一般行为及体质量变化,测定血清尿素氮(BUN)和肌酐(SCr)的含量及肾脏中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、一氧化氮(NO)的含量,HE染色观察组织病理变化。结果:与空白组相比,模型组大鼠精神萎靡,活动迟缓,常埋头蜷缩,部分大鼠甚至出现了拒食,大便溏稀,肛周毛发较湿且脏乱不整的现象;各给药组较模型组情况明显好转。麻黄水提物低剂量组大鼠体质量明显增加,与模型组相比,差异有统计学意义(P <0. 05或P <0. 01);各给药组大鼠体质量增加与剂量呈正相关。与模型组相比,麻黄水提物低剂量组大鼠肾脏系数和BUN差异无统计学意义(P> 0. 05),麻黄水提物中、高剂量组大鼠SCr和MDA显著降低,SOD和GSH显著增加(P <0. 05或P <0. 01),低剂量组大鼠SCr显著降低(P <0. 01),高剂量组大鼠NO显著降低(P <0. 05)。与低剂量组相比,麻黄水提物中、高剂量组SCr显著降低(P <0. 01)。病理结果显示,模型组大鼠肾小管蛋白管型,炎性细胞浸润,肾间质充血,肾小管上皮细胞出现明显的浑浊性肿胀,麻黄水提物干预后上述现象明显减轻甚至消失。结论:麻黄水提物能保护顺铂导致的大鼠肾脏损伤,并且高剂量组效果最好。
Objective: To explore the effects of ephedra water extract on renal injury induced by cisplatin in rats. Methods: The rats were randomly divided into 5 groups: the blank group,the model group,and ephedra water extract high(400 mg·kg~(-1)),middle(200 mg·kg~(-1)) and low(100 mg·kg~(-1)) dose groups with 8 rats in each. The blank group and the model group were given saline once daily(1 ml/100 g),and medication administration groups were given ephedra water extract once daily. The treatment course was10 days. The rats in the model group and ephedra water extract groups were given cisplatin(8 mg·kg~(-1)) in the morning on the sixth day. The changes of general behavior and body weight of rats were observed,the contents of BUN and SCr in serum and the contents of SOD,MDA,GSH and NO in kidney were determined,and histopathological changes were observed by HE staining. Results: Compared with those in the blank group,the rats in the model group showed obvious mental malaise,slow movement,often crouched with heads buried,and some rats even appeared the phenomenon of resisting food,defecating sugar thinly,and wet and messy hair around the anus. The drug administration groups were significantly better than the model group. The body weight of the rats in low dose group with ephedrine water extract increased significantly when compared with that in the model group,and the difference was statistically significant( P < 0. 05 or P < 0. 01). The increase of body mass in each administration group was positively correlated with the dose. Compared with those in the model group,the kidney coefficient and BUN showed no significant differences in low-dose ephedrine water extract dose group( P > 0. 05),SCr and MDA were significantly decreased in water extract middle and high dose groups,SOD and GSH were significantly increased( P < 0. 05 or P < 0. 01),SCr was significantly decreased in the low dose group( P < 0. 01),and NO was significantly decreased in high dose group( P < 0. 05). Compared with that in the low dose group,SCr was significantly lower in water extract middle and high dose groups( P < 0. 01). The pathological results showed that tubule protein type,inflammatory cell infiltration,interstitial hyperemia and tubule epithelial cells were observed in the model group. The above phenomena were obviously alleviated or even disappeared after the intervention of ephedra water extract. Conclusion: Ephedra water extract can protect kidney injury induced by cisplatin in rats,and its high dose exhibits the best effect.
Objective: To explore the effects of ephedra water extract on renal injury induced by cisplatin in rats. Methods: The rats were randomly divided into 5 groups: the blank group,the model group,and ephedra water extract high(400 mg·kg~(-1)),middle(200 mg·kg~(-1)) and low(100 mg·kg~(-1)) dose groups with 8 rats in each. The blank group and the model group were given saline once daily(1 ml/100 g),and medication administration groups were given ephedra water extract once daily. The treatment course was10 days. The rats in the model group and ephedra water extract groups were given cisplatin(8 mg·kg~(-1)) in the morning on the sixth day. The changes of general behavior and body weight of rats were observed,the contents of BUN and SCr in serum and the contents of SOD,MDA,GSH and NO in kidney were determined,and histopathological changes were observed by HE staining. Results: Compared with those in the blank group,the rats in the model group showed obvious mental malaise,slow movement,often crouched with heads buried,and some rats even appeared the phenomenon of resisting food,defecating sugar thinly,and wet and messy hair around the anus. The drug administration groups were significantly better than the model group. The body weight of the rats in low dose group with ephedrine water extract increased significantly when compared with that in the model group,and the difference was statistically significant( P < 0. 05 or P < 0. 01). The increase of body mass in each administration group was positively correlated with the dose. Compared with those in the model group,the kidney coefficient and BUN showed no significant differences in low-dose ephedrine water extract dose group( P > 0. 05),SCr and MDA were significantly decreased in water extract middle and high dose groups,SOD and GSH were significantly increased( P < 0. 05 or P < 0. 01),SCr was significantly decreased in the low dose group( P < 0. 01),and NO was significantly decreased in high dose group( P < 0. 05). Compared with that in the low dose group,SCr was significantly lower in water extract middle and high dose groups( P < 0. 01). The pathological results showed that tubule protein type,inflammatory cell infiltration,interstitial hyperemia and tubule epithelial cells were observed in the model group. The above phenomena were obviously alleviated or even disappeared after the intervention of ephedra water extract. Conclusion: Ephedra water extract can protect kidney injury induced by cisplatin in rats,and its high dose exhibits the best effect.
引文
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8 Shanshan L,Xian QM,Zhi BW,et al.Polysaccharide from Ephedra sinica Stapf inhibits inflammation expression by regulating Factor-1/Smad2 signaling[J].Int J Biol Macromol,2018,106:947-954
9 Aydinoz S,Uzun G,Cermik H,et al.Effects of different doses of hyperbaric oxygen on cisplatin-induced nephrotoxicity[J].Ren Fail,2007,29(3):257-263
10 Chen Q,Peng H,Dong L,et al.Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity[J].Int Immunopharmacol,2016,36:1-8
2 Dasari S,Tchounwou PB.Cisplatin in cancer therapy:molecular mechanisms of action[J].Eur J Pharmacol,2014,740:364-378
3 Hao Q,Xiao X,Zhen J,et al.Resveratrol attenuates acute kidney injury by inhibiting death receptor mediated apoptotic pathways in a cisplatin induced rat model[J].Mol Med Report,2016,14(14):3683-3689
4 Pabla N,Dong Z.Cisplatin nephrotoxicity:mechanismsand renoprotective strategies[J].Kidney Int,2008,73(9):994-1007
5王国柱.麻黄干浸膏及其单宁成分治疗慢性肾功能衰竭的实验研究[J].中国中西医结合杂志,1994,14(8):485-488
6张连茹,邹国林,杨天鸣,等.麻黄水溶性多糖的提取及其清除氧自由基作用的研究[J].氨基酸和生物资源,2000,22(3):24-26
7陈荣民,朱耕新,许芝银,等.麻黄种不同提取物对细胞免疫的影响[J].南京中医药大学学报,2001,17(4):234-236
8 Shanshan L,Xian QM,Zhi BW,et al.Polysaccharide from Ephedra sinica Stapf inhibits inflammation expression by regulating Factor-1/Smad2 signaling[J].Int J Biol Macromol,2018,106:947-954
9 Aydinoz S,Uzun G,Cermik H,et al.Effects of different doses of hyperbaric oxygen on cisplatin-induced nephrotoxicity[J].Ren Fail,2007,29(3):257-263
10 Chen Q,Peng H,Dong L,et al.Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity[J].Int Immunopharmacol,2016,36:1-8