【摘要】 目的 观察扶正化结汤对二乙基亚硝胺（DEN）诱导的肝细胞癌模型大鼠肝组织的保护作用，并探讨其作用机制。方法 SPF级雄性WISTAR大鼠30只随机数字表法分为正常对照组、模型组和治疗组，每组10只。各组大鼠均以普通饲料喂养。模型组和治疗组予以DEN皮下注射50 mg/kg·次，每周1次，连续17周，建立肝细胞癌模型。正常对照组予以生理盐水0.4 m L/100 g腹腔注射，每周1次。造模开始即连续灌胃给药干预，正常对照组和模型组均给予生理盐水1 m L/100 g灌胃，1天1次；治疗组给予扶正化结汤按1 m L/100 g灌胃，每天1次，连续17周。检测大鼠血清中丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、白介素6(IL-6)、甲胎蛋白（AFP）及核转录因子κB(NF-κB)水平，比较各组体质量、肝质量、肝脏系数，分析病理学表现，实时荧光定量RT-PCR检测大鼠肝组织NF-κB表达。结果 与正常对照组比较，模型组大鼠体质量下降[（262.78±27.61）g比（389.51±29.48）g,P<0.01]，肝脏质量及肝脏系数上升[（21.31±2.84）g比（8.25±0.84）g、（8.10±0.42）%比（2.12±0.08）%,P均<0.01]。模型组ALT、AST、IL-6、AFP、NF-κB水平均明显升高[（225.60±21.77）U/L比（36.64±4.07）U/L、（248.36±26.26）U/L比（84.56±3.75）U/L、（100.26±14.88）pg/m L比（64.11±18.30）pg/m L、（10.83±1.15）ng/m L比（9.01±1.32）ng/m L、（12.54±1.74）ng/m L比（10.15±1.29）ng/m L,P均<0.01]。与模型组比较，治疗组大鼠体质量无明显变化[（254.10±23.06）g比（262.78±27.61）g,P>0.05]，肝脏质量及肝脏系数显著下降[（17.11±2.56）g比（21.31±2.84）g、（6.74±0.74）%比（8.10±0.42）%,P<0.01]；治疗组ALT、AST、IL-6、AFP、NF-κB水平均有下降[（176.49±29.09）U/L比（225.60±21.77）U/L、（203.70±49.49）U/L比（248.36±26.26）U/L、（80.81±22.55）pg/m L比（100.26±14.88）pg/m L、（8.22±1.45）ng/m L比（10.83±1.15）ng/m、（9.90±1.74）ng/m L比（12.54±1.74）ng/m L,P<0.05或P<0.01]。HE染色病理显示，模型组大鼠肝组织，癌症细胞巢形成，细胞坏死、变性；治疗组大鼠肝组织癌细胞巢形成和细胞坏死减少。RT-PCR显示，模型组NF-κB水平较正常对照组升高[（2.19±1.06）比（1.00±0.00）,P<0.01]，治疗组NF-κB水平较模型组下降[（1.69±0.48）比（2.19±1.06）,P<0.05]。结论 扶正化结汤可能通过下调升高的NF-κB水平抑制大鼠肝脏炎症、癌细胞增殖，促进模型大鼠肝癌细胞凋亡，从而改善其肝功能。更多还原

【Abstract】 Objective To assess the protective effect of Fuzheng Huajie Decoction on a rat model of diethylnitrosamine(DEN)-induced hepatocellular carcinoma(HCC) and then to explore the underlying molecular events.Methods Thirty specific pathogen-free(SPF)-grade male Wistar rats were fed with ordinary diet and then randomly divided into normal control, model control, and treatment groups(n=10 per group). The normal control rats were intraperitoneally injected with normal saline(0.4 m L/100 g) once a week for 17 weeks, whereas the model and treatment groups of rats were subcutaneously injected with DEN(50 mg/kg) once a week for 17 weeks to establish the HCC model, during this period of time, the normal and model control rats were intragastrically given normal saline(1 m L/100 g), but the treatment group of rats was intragastrically given Fuzheng Huajie Decoction(1 m L/100 g)daily for consecutive 17 weeks. Serum levels of the aalanine aminotransferase(ALT), aspartate aminotransferase(AST), interleukin-6(IL-6), alpha-fetoprotein(AFP), and nuclear transcription factor κB(NF-κB) were assayed,while the body weight, liver weight, and liver coefficient of each rat were taken and compared for the pathological changes and NF-κB expression in rat liver tissues were analyzed using RT-q PCR. Results Compared with normal control rats, the body weight was reduced(262.78±27.61 vs. 389.51±29.48 g; P<0.01), whereas the liver weight and liver index were increased in model rats(21.31 ±2.84 vs. 8.25±0.84 g and 8.10±0.42 vs. 2.12±0.08%, respectively;P<0.01). Moreover, compared with normal control rats, the serum level of ALT, AST, IL-6, AFP, and NF-κB was significantly increased in model rats(225.60±21.77 vs. 36.64±4.07 U/L, 248.36±26.26 vs. 84.56±3.75 U/L, 100.26±14.88 vs. 64.11±18.30 pg/m L, 10.83±1.15 vs. 9.01±1.32 ng/m L, and 12.54±1.74 vs. 10.15±1.29 ng/m L, respectively;P<0.01). Although the body weight of treatment group of rats didn’t have a significant change compared with model rats(254.10±23.06 vs. 262.78±27.61 g; P>0.05), the liver weight and liver index were decreased after treatment(17.11±2.56 vs. 21.31±2.84 g and 6.74±0.74 vs. 8.10±0.42%, respectively; P<0.01). The treatment also reduced serum levels of ALT, AST, IL-6, AFP, and NF-κB compared with those of the model controls(176.49±29.09 vs.225.60±21.77 U/L, 203.70±49.49 vs. 248.36±26.26 U/L, 80.81±22.55 vs. 100.26±14.88 pg/m L, 8.22±1.45 vs. 10.83±1.15 ng/m L, and 9.90±1.74 vs. 12.54±1.74 ng/m L, respectively; P<0.05 or P<0.01). H&E staining showed that the model rats formed the HCC cell nests and cell necrosis and degeneration in liver tissues, whereas the treatment reduced formation of HCC cell nests and cell necrosis in liver tissues. In addition, the RT-PCR data showed that liver tissue level of NF-κB was higher in model rats than that in normal control rats(2.19±1.06 vs. 1.00±0.00; P<0.01), whereas tissue level of NF-κB was lower in treatment rats than that in model rats(1.69±0.48 vs. 2.19±1.06;P<0.05). Conclusion The Fuzheng Huajie Decoction was able to improve liver function and prevent liver inflammation and HCC cell proliferation but promote them to undergo apoptosis in the rat HCC model.更多还原