摘要
目的探索芹菜素(APG)对顺铂(DDP)化疗所致肾损伤大鼠的保护作用及机制研究。方法将60只SD大鼠随机分为空白组、模型组、氨磷汀组(阳性对照组)及APG低、中、高剂量组,每组10只。模型组、氨磷汀组及APG低、中、高剂量组大鼠均采用一次性腹腔注射DDP(7.5 mg·kg^(-1))的方法建立DDP致肾损伤大鼠模型,空白组大鼠仅腹腔注射生理盐水(不造模);然后分别腹腔注射给药(APG低、中、高剂量组分别给予10、20、40 mg·kg^(-1)APG,氨磷汀组给予1 mg·kg^(-1)氨磷汀,空白组和模型组均给予生理盐水),1次/d,连续给药28 d。测定各组大鼠24 h尿蛋白量和血清肌酐(Scr)、尿素氮(BUN)含量,HE染色法、TUNEL法分别行肾脏病理学检查和细胞凋亡检测,生化分析法检测MDA含量和抗氧化酶(SOD、GSH-Px)活性,ELISA法检测炎症细胞因子(TNF-α、IL-1β、IL-6)水平,Western blotting检测核因子E2相关因子2(Nrf2)、血红素加氧酶-1(HO-1)、核因子-κB(NF-κB)、激活型半胱胺酸蛋白酶-3(Cleaved Caspase-3)蛋白的表达水平。结果与模型组比较,APG中、高剂量组和氨磷汀组大鼠24 h尿蛋白量和血清Scr、BUN含量显著降低(P<0.05),肾脏组织病理学改变和细胞凋亡状况明显改善,凋亡指数(AI)显著降低(P<0.01),MDA含量显著降低且SOD、GSH-Px活性显著升高(P<0.05),TNF-α、IL-1β、IL-6水平显著降低(P<0.05),Nrf2、HO-1表达显著上调而NF-κB、Cleaved Caspase-3表达显著下调(P<0.01)。与氨磷汀组比较,APG高剂量组大鼠血清Scr、BUN含量显著降低(P<0.05),肾脏组织病理学改变和细胞凋亡状况明显改善、AI显著降低(P<0.01),MDA含量显著降低且SOD活性显著升高(P<0.01),TNF-α、IL-1β水平显著降低(P<0.05),Nrf2、HO-1表达显著上调且Cleaved Caspase-3表达显著下调(P<0.05)。结论 APG对DDP所致肾损伤大鼠具有保护作用,其作用机制可能与激活Nrf2/HO-1通路而抑制氧化应激损伤、炎症反应和细胞凋亡有关�
ObjectiveTo investigate the protective effects and mechanism of apigenin(APG) on cisplatin(DDP) chemotherapy-induced renal injury in rats.MethodsSixty SD rats were randomly divided into blank group, model group, APG low-, medium-, high-dose groups and amifostine group, 10 in each group. The rats in model group, APG low-, medium-,high-dose groups and amifostine group were given DDP(7.5 mg·kg^(-1)) once by intraperitoneal injection to make the model of DDP-induced renal injury. The rats in blank group were given normal saline(NS). And then the drugs were administered intraperitoneally once a day for 28 days. The rats in APG low-, middle-and high-dose groups were given 10, 20, 40 mg·kg^(-1) APG separately, and those in amifostine group was given 1 mg·kg^(-1) amifostine, and those in blank group and model group were given NS. The 24 h urine protein and the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) were detected. The pathological change of renal tissue was examined by HE staining and the apoptosis was observed by TUNEL.The level of malondialdehyde(MDA) and the activity of antioxidant enzymes(SOD, GSH-Px) were detected by biochemical analysis. The levels of inflammatory cytokines(TNF-α, IL-1β, IL-6) were detected by ELISA. The expression of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase-1(HO-1), nuclear factor-κB(NF-κB), and cleaved caspase-3 were determined by Western blotting.ResultsCompared with the model group, the 24 h urine protein and Scr and BUN levels of the rats in APG medium-, high-dose group and amifostine group were decreased(P<0.05);the renal histopathological changes and apoptosis were significantly improved, and the AI were decreased(P<0.01);the MDA level was decreased,while the activity of SOD and GSH-Px was increased(P<0.05);the levels of TNF-α, IL-1β and IL-6 were significantly decreased(P<0.05);the expression of Nrf2 and HO-1 were up-regulated, while the expression of NF-κB and cleaved caspase-3 were down-regulated(P<0.01). Compared with the amifostine
作者
周莎莎
郭志远
杨智勇
付吕平
张贵平
ZHOU Shasha;GUO Zhiyuan;YANG Zhiyong;FU Lüping;ZHANG Guiping(Handan Central Hospital,Handan 056001,China)
出处
《肿瘤药学》
CAS
2021年第5期554-560,共7页
Anti-Tumor Pharmacy
基金
河北省医学科学研究课题计划(20191843)。
