文献类型：期刊文献

中文题名：敦煌平胃丸联合顺铂对SCG-7901胃癌荷瘤小鼠的抑瘤作用及肾毒性研究

英文题名：Effect of Dunhuang Pingwei Pill Combined with Cisplatin on Tumor Inhibition and Renal Toxicity in Mice with SCG-7901 Gastric Cancer

作者：舍雅莉[1];赵晓文[1];李俊杰[1];张国欣[1];刘永琦[1];段永强[1];李长天[1];李亚玲[1]

第一作者：舍雅莉

机构：[1]甘肃中医药大学,敦煌医学与转化教育部重点实验室,兰州730000

第一机构：甘肃中医药大学科研实验中心（甘肃省中医药标准化技术委员会秘书处）

年份：2021

卷号：37

期号：2

起止页码：13

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：甘肃省高等学校创新能力提升资助项目(编号:2019A-074);敦煌医学与转化教育部重点实验室开放课题(编号:DHYX14-010、DHYX18-012)。

语种：中文

中文关键词：敦煌平胃丸;胃癌;肾毒性;核因子E2相关因子2;血红素氧合酶-1;顺铂;减毒

外文关键词：Dunhuang Pingwei pill;gastric cancer;renal toxicity;Nrf2;HO-1;cisplatin;reducing toxicity

摘要：目的:研究敦煌古方平胃丸联合顺铂对SCG-7901胃癌荷瘤小鼠的抑瘤作用及对肾脏毒性影响,探讨敦煌平胃丸联合顺铂对降低肾毒性的作用机制。方法:建立小鼠SCG-7901胃癌皮下荷瘤模型,接种第8 d随机分为模型对照组、顺铂2×10^(-3) g/kg组、平胃丸14.04 g/kg+顺铂2×10^(-3) g/kg组、平胃丸14.04 g/kg组,连续给药10 d,隔日小鼠称重并观察一般情况;末次给药后剥取肿瘤、肾,计算抑瘤率和肾指数,苏木素-伊红(HE)染色观察肾组织病理变化;检测血清中肌酐(Scr)、尿素氮(BUN)含量,肾组织中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量;蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)分别检测肾组织核因子E2相关因子2(Nrf2)、血红素氧合酶-1(HO-1)蛋白和mRNA的表达。结果:接种后第12 d开始,与模型对照组比较,顺铂2×10^(-3) g/kg、平胃丸14.04 g/kg+顺铂2×10^(-3) g/kg组体质量明显下降(P<0.05或P<0.01),与顺铂2×10^(-3) g/kg组比较,平胃丸14.04 g/kg+顺铂2×10^(-3) g/kg组体质量明显升高(P<0.05或P<0.01);顺铂2×10^(-3) g/kg、平胃丸14.04 g/kg+顺铂2×10^(-3) g/kg、平胃丸14.04 g/kg组抑瘤率分别为63.84%、70.57%和30.74%,瘤重均较模型对照组显著降低(P<0.01),与模型对照组比较,各给药组肾脏均有不同程度病理损伤,其中,顺铂2×10^(-3) g/kg组最为明显;顺铂2×10^(-3) g/kg组肾指数、Scr、BUN和MDA含量显著升高(P<0.01),SOD活性、Nrf2、HO-1蛋白和mRNA表达显著下降(P<0.01)。与顺铂2×10^(-3) g/kg组比,平胃丸14.04 g/kg+顺铂2×10^(-3) g/kg组肾指数、Scr、BUN和MDA含量明显下降(P<0.05或P<0.01),SOD活性、Nrf2、HO-1蛋白和mRNA表达显著升高(P<0.05或P<0.01)。结论:敦煌平胃丸与顺铂单独和联合使用均对SCG-7901胃癌荷瘤小鼠具有抑瘤作用;敦煌平胃丸联合顺铂可能通过激活Nrf2/HO-1信号通路,增强细胞抗氧化应激能力,从而降低顺铂对肾脏的毒性损伤,起到减毒作用。
Objective: To study the antitumor effect of Dunhuang Pingwei pill combined with cisplatin on SCG-7901 gastric cancer-mice and its toxic effect on kidney, and to explore the mechanism of its reducing renal toxicity. Methods: The subcutaneous tumor bearing model of SCG-7901 gastric cancer in mice was established. On the 8 th day of inoculation, the mice were randomly divided into the model group, cisplatin group(2×10^(-3) g/kg), Pingwei pill + cisplatin group(14.04 g/kg+2×10^(-3) g/kg) and Pingwei pill group(14.04 g/kg). Mice were administered for 10 consecutive days, on 11 th day, mice were weighed and general conditions were observed. The tumor and kidney were collected and weighed to calculate the anti-tumor rate and renal index, the pathological change of kidney was observed by hematoxylin-Eosin(HE) staining. The levels of creatinine(Scr), urea nitrogen(BUN) in serum and superoxide dismutase(SOD), malondialdehyde(MDA) in renal tissues were detected. The mRNA and protein of nuclear factor erythroid-2-related factor 2(Nrf2) and heme oxygenase-1(HO-1) in renal tissues were detected by real-time PCR and Western blot. Results: On the 12 th day after inoculation, compared with the model group, the body mass of mice in cisplatin group(2×10^(-3) g/kg) and Pingwei pill + cisplatin group(14.04 g/kg+2×10^(-3) g/kg) were decreased significantly(P<0.05 or P<0.01). Compared with cisplatin group(2×10^(-3) g/kg), the body mass in Pingwei pill + cisplatin group(14.04 g/kg+2×10^(-3) g/kg) was significantly increased(P<0.05 or P<0.01). The tumor inhibition rates in cisplatin group(2×10^(-3) g/kg), Pingwei pill + cisplatin group(14.04 g/kg+2×10^(-3) g/kg) and Pingwei pill group(14.04 g/kg) were 63.84%, 70.57% and 30.74%, respectively. Compared with the model group, the tumor weight in each administration group was significantly decreased(P<0.01), different degrees of pathological damage of kidneys were observed in all drug treatment groups, while it in cisplatin group(2×10^(-3) g/kg) was the most obvious. Compared with the model group, the renal index, the contents of Scr, BUN and MDA in the cisplatin group(2×10^(-3) g/kg) were significantly increased(P<0.01), the SOD activity, the mRNA and protein expressions of Nrf2 and HO-1 were significantly decreased(P<0.01). Compared with the cisplatin group(2×10^(-3) g/kg), the renal index, Scr, BUN and MDA contents in Pingwei pill + cisplatin group(14.04 g/kg+2×10^(-3) g/kg) were significantly decreased(P<0.05 or P<0.01), while SOD activity, the mRNA and protein expression of Nrf2 and HO-1 were significantly increased(P<0.05 or P<0.01). Conclusion: Dunhuang Pingwei Pill and its combination with cisplatin have the tumor suppressive effect in SCG-7901 tumor-bearing mice. Dunhuang Pingwei Pill combined with cisplatin may enhance the anti-oxidative stress ability by activating the Nrf2/HO-1 signaling pathway, thus reducing the cisplatin induced kidney injury, it plays a role of reducing toxicity.