摘要
目的探讨鳖甲煎丸治疗肝癌前病变的可能作用机制。方法30只雄性Wistar大鼠随机分为正常组、模型组、鳖甲煎丸组,每组10只。除正常组外其余两组注射二乙基亚硝胺(DEN)连续16周建立肝癌前病变模型。造模第8周,鳖甲煎丸组给予鳖甲煎丸药液1.1 g/kg灌胃,正常组和模型组予以10 ml/kg生理盐水灌胃,均每日1次,连续灌胃至第18周。给药结束后测量大鼠体重、肝脏重量、肝脏表面结节数量及最大结节直径,观察肝脏病理改变及肝组织甲胎蛋白(AFP)、人胎盘型谷胱甘肽S-转移酶(GST-π)表达情况,检测肝功能指标包括丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、总胆红素(TBiL)、白蛋白(ALB)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP),血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、趋化因子2(CCL-2)表达,肝组织IL-6、TNF-α、CCL-2 mRNA表达及IL-6、TNF-α、磷酸化转录激活因子3(p-STAT3)蛋白表达。结果与正常组比较,模型组大鼠体重明显降低,肝脏重量及肝脏体重比均明显增加,肝脏表面结节数量及结节最大直径明显增加,HE染色见肿瘤病灶内出现大片肝细胞坏死,肿瘤细胞异型性明显,不典型增生结节内GST-π呈强阳性,瘤组织中AFP染色明显,肝功能指标除ALB外均明显升高,血清IL-6、CCL-2水平,肝组织IL-6、CCL-2mRNA表达及IL-6、TNF-α、p-STAT3蛋白相对表达量均明显升高(P<0.01);与模型组比较,鳖甲煎丸组肝脏重量、肝脏体重比均明显下降,肝脏表面结节数量及结节最大直径明显降低,癌细胞多呈高分化,肿瘤坏死区少见,GST-π、AFP染色较浅,阳性区域较少,血清AST、TBiL、GGT水平明显降低,血清IL-6、CCL-2水平,肝组织IL-6、CCL-2 mRNA表达及IL-6、p-STAT3蛋白相对表达量均明显降低(P<0.05或P<0.01)。结论鳖甲煎丸可能通过降低炎症因子表达,抑制IL-6/STAT3通路的激活,从而抑制肝癌前病变的发生发展。
Objective To explore the possible mechanism of Biejiajian Pills(鳖甲煎丸)in the treatment of precancerous lesions of liver.Methods Thirty male Wistar rats were randomly divided into normal group,model group,and Biejiajian Pills group,with 10 rats in each group.Except for the normal group,the rats in the other two groups were injected with diethylnitrosamine(DEN)for 16 consecutive weeks to establish liver precancerous lesion models.On the 8th week of modelling,the liquid of Biejiajian Pills(1.1 g/kg)was given by gavage to the Beijiajian Pills group,while normal saline(10 ml/kg)was administered by gavage in the normal group and the model group;the interventions were all given once daily until Week 18.After the administration,the body weight of the rats,the weight of the liver,the number of nodules on the liver surface and the largest nodule diameter were measured;the pathological changes of the liver and the expression of alpha-fetoprotein(AFP)and human placental glutathione S-transferase(GST-π)in the liver tissue were assessed;the levels of liver function indicators including alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBiL),albumin(ALB),glutamyl transfer Peptidase(GGT),alkaline phosphatase(ALP),serum interleukin 6(IL-6),tumor necrosis factorα(TNF-α)and chemokine 2(CCL2),the mRNA expression of IL-6,TNF-αand CCL2,as well as the protein expression of IL-6,TNF-αand phosphorylated transcription activator 3(p-STAT3)in the liver tissue were detected.Results Compared to those in the normal group,the body weight of the rats in the model group was significantly reduced;the liver weight and the ratio of liver vs body weight were significantly increased;the number of nodules on the liver surface and the largest nodule diameter were significantly increased;HE staining showed large areas of hepatocyte necrosis in the tumor lesions and obvious atypia of cancer cells;GST-πin dysplastic nodules was strongly positive;obvious AFP staining was shown in tumor tissues;all liver function indi
作者
陈炜聪
文彬
孙海涛
孙嘉玲
杨雪梅
黄少慧
安海燕
庞杰
贺松其
CHEN Weicong;WEN Bin;SUN Haitao;SUN Jialing;YANG Xuemei;HUANG Shaohui;AN Haiyan;PANG Jie;HE Songqi(School of Chinese Medicine,Southern Medical University,Guangzhou,510515;PLA Southern Theater Command Air Force Hospital)
出处
《中医杂志》
CSCD
北大核心
2021年第19期1720-1727,共8页
Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81774037)
广东省自然科学基金(2021A1515012591)。
关键词
原发性肝细胞癌
癌前病变
鳖甲煎丸
白细胞介素6
转录激活因子3
hepatocellular carcinoma
precancerous lesions
Biejiajian Pills(鳖甲煎丸)
interleukin 6
transcription activator 3
