机构地区:[1]青海省交通医院泌尿外科,西宁市810008 [2]郑州大学第一附属医院泌尿外科,河南省郑州市450000 [3]青海大学附属医院泌尿外科,西宁市810008
出 处:《广西医学》2021年第20期2436-2440,2446,共6页Guangxi Medical Journal
基 金:河南省卫生计生科技英才海外研修工程项目(LHGJ20190182);青海大学中青年科研基金项目(2018-QYY-11)。
摘 要:目的探讨姜黄素对膀胱癌大鼠组织病理学变化、炎症反应和氧化应激反应的影响。方法将93只雄性SD大鼠随机分为对照组(n=20)、模型组(n=25)、60 mg/kg姜黄素组(n=24)和120 mg/kg姜黄素组(n=24)。除对照组外,其余组大鼠采用N-丁基-N-(4-羟丁基)亚硝基胺灌胃建立膀胱癌模型。第一次灌胃前7 d,给予不同剂量姜黄素组大鼠相应剂量的200μL姜黄素灌胃,1次/d,持续8周,其他两组给予相同剂量的生理盐水灌胃。之后4组大鼠均连续给予200μL生理盐水灌胃8个月。干预8个月后,检测4组大鼠血清炎症指标[白细胞介素1β(IL-1β)、C反应蛋白(CRP)、转化生长因子β1(TGF-β1)]以及氧化应激指标[一氧化氮、丙二醛、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)]水平,并观察大鼠膀胱组织的病理学变化。结果(1)干预8个月后,对照组大鼠的膀胱组织正常,而模型组和不同剂量姜黄素组大鼠的膀胱组织出现程度不同的癌变,但与模型组相比,60 mg/kg姜黄素组大鼠膀胱组织的细胞层次变少,120 mg/kg姜黄素组大鼠膀胱组织中部分细胞形态规则并且表现为不典型增生;120 mg/kg姜黄素组非浸润性膀胱尿路上皮癌的比例高于模型组,而浸润性膀胱尿路上皮癌的比例低于模型组(P<0.05)。(2)模型组大鼠血清IL-1β、CRP、TGF-β1、一氧化氮、丙二醛水平均高于对照组,血清SOD、T-AOC水平均低于对照组(均P<0.05);60 mg/kg姜黄素组、120 mg/kg姜黄素组大鼠血清IL-1β、CRP、TGF-β1、一氧化氮及丙二醛水平均低于模型组,血清SOD、T-AOC水平均高于模型组,且120 mg/kg姜黄素组大鼠血清IL-1β、CRP、TGF-β1、一氧化氮及丙二醛水平均低于60 mg/kg姜黄素组,血清SOD、T-AOC水平均高于60 mg/kg姜黄素组(均P<0.05)。结论姜黄素能够抑制膀胱癌大鼠的组织病理学进展,这可能与其抑制机体炎症反应和氧化应激反应有关,且大剂量(120 mg/kg)姜黄素的效果更佳。Objective To explore the effects of curcumin on histopathological changes,inflammatory reactions,and oxidative stress reactions in rats with bladder cancer.Methods Ninety-three male SD rats were randomly divided into control group(n=20),model group(n=25),60 mg/kg curcumin group(n=24)and 120 mg/kg curcumin group(n=24).Except the control group,rats in the remaining groups were administrated N-butyl-N-(4-hydroxybuty1)nitrosamine by gavage to develop the models of bladder cancer.Rats in the different doses curcumin groups were given the corresponding dose of curcumin(200μL)once daily by gavage for eight consecutive weeks since day 7 before the first intragastric administration,and the other two groups were given isodose normal saline by gavage.Then rats in the four groups were given 200μg normal saline by gavage for eight consecutive months.After eight months of the intervention,the serum levels of inflammation indicators(interleukin 1β[IL-1β],C-reactive protein[CRP],transforming growth factorβ1[TGF-β1])and oxidative stress indicators(nitric oxide,malondialdehyde,superoxide dismutase[SOD],total antioxidant capacity[T-AOC])were detected in the four groups,and the pathological changes in rat bladder tissues were observed.Results(1)After eight months of the intervention,rat bladder tissues were normal in the control group,whereas showed different degrees of carcinogenesis in the model group and different doses curcumin groups;however,compared with the model group,rats in the 60 mg/kg curcumin group had fewer cellular layers in bladder tissues,and rats in the 120 mg/kg curcumin group had some cells in bladder tissues with regular morphology and presented as atypical hyperplasia;the 120 mg/kg curcumin group yielded a higher proportion of rats with noninvasive urothelial carcinoma of the bladder,and a lower proportion of rats with invasive urothelial carcinoma of the bladder as compared with the model group(P<0.05).(2)Rats in the model group exhibited higher serum levels of IL-1β,CRP,TGF-β1,nitric oxide,and malondi
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