浙江中西医结合杂志

.扶正化结汤对二乙基亚硝胺诱导的肝细胞癌模型大鼠肝组织保护机制研究[J].浙江中西医结合杂志,2023,33(4):

扶正化结汤对二乙基亚硝胺诱导的肝细胞癌模型大鼠肝组织保护机制研究

Protective effect and mechanism of Fuzheng Huajie Decoction on rat hepatocellular carcinoma

投稿时间：2022-07-18 修订日期：2023-03-01

DOI：

英文关键词:Rat Hepatocellular carcinoma Diethylnitrosamine NF-κB Fuzheng Huajie Decoction

基金项目:名称:1.浙江省中医药管理局项目:基于“活血渗湿”治法的中西医结合逆转肝纤维化真实世界研究(项目编号:2022ZA144)。2.萧山区科学技术局项目:NF-κB在PHC大鼠肝组织中的表达及扶正化结汤对其的影响(项目编号:2019221)。

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中文摘要:

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 mL/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 mL/100 g灌胃，1天1次；治疗组给予扶正化结汤按1 mL/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/mL比（64.11±18.30） pg/mL、（10.83±1.15） ng/mL比（9.01±1.32） ng/mL、（12.54±1.74） ng/mL比（10.15±1.29） ng/mL，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/mL比（100.26±14.88） pg/mL、（8.22±1.45） ng/mL比（10.83±1.15） ng/mL、（9.90±1.74） ng/mL比（12.54±1.74） ng/mL，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。

英文摘要:

ABSTRACT Objective To observe the protective effect of Fuzheng Huajie Decoction on diethylnitrosamine (DEN) -induced hepatocellular carcinoma (HCC) in rats, and to explore its mechanism. Methods Thirty SPF male WISTAR rats were randomly divided into three groups, normal control group, model group and treatment group, with 10 rats in each group. All groups were fed with ordinary diet. Normal control group was intraperitoneal injection of normal saline 0.4mL/100g, once a week. Model group and treatment group were subcutaneous injection of DEN 50mg/kg·every time, once a week for 17 weeks to establish the model of HCC. Normal control group and model group were given normal saline 1mL/100g intragastric administration once a day. Treatment group was given Fuzheng Huajie Decoction (1mL /100g), once a day, for consecutive 17 weeks. The levels of Aalanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), alpha-fetoprotein (AFP) and nuclear transcription factor κB (NF-κB) in serum of rats were detected, and the body weight, liver weight and liver coefficient of each group were compared. The pathological manifestations were analyzed and the expression of NF-κB in liver tissues of rats was detected by RT-PCR. Results Compared with normal control group, body weight of rats in model group decreased (262.78±27.61 vs. 389.51±29.48 g, P<0.01), liver weight and liver index increased (21.31±2.84 vs. 8.25±0.84 g, 8.10±0.42 vs. 2.12±0.08%, P<0.01). Compared with normal control group, ALT, AST, IL-6, AFP and NF-κB levels in model group were significantly increased (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/mL, 10.83±1.15 vs. 9.01±1.32 ng/mL, 12.54±1.74 vs.10.15±1.29 ng/mL, P<0.01). Compared with model group, there was no significant difference in body weight between treatment group and model group (254.10±23.06 vs. 262.78±27.61 g, P>0.05), but liver weight and liver index in treatment group decreased (17.11±2.56 vs. 21.31±2.84 g, 6.74±0.74 vs. 8.10±0.42%, P<0.01). After treatment with Fuzheng Huajie Decoction, the levels of ALT, AST, IL-6, AFP and NF-κB in treatment group were decreased compared with model group (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/mL, 8.22±1.45 vs. 10.83±1.15 ng/mL, 9.90±1.74 vs. 12.54±1.74 ng/mL, P<0.05, P<0.01). HE pathological staining showed that nests of cancer cells were formed, cell necrosis and degeneration in liver tissue of rats in model group. After treatment with Fuzheng Huajie Decoction, nest formation of cancer cells and cell necrosis were reduced in liver tissue of rats in treatment group. RT-PCR showed that the level of NF-κB in model group was higher than that in normal control group (2.19±1.06 vs. 1.00±0.00, P<0.01), and the level of NF-κB in treatment group was lower than that in model group after treatment with Fuzheng Huajie Decoction (1.69±0.48 vs. 2.19±1.06, P<0.05). Conclusion Fuzheng Huajie Decoction can inhibit liver inflammation and proliferation of cancer cells, promote apoptosis of hepatoma cells in model rats, and improve liver function by down-regulating NF-κB level.

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