摘要
目的:研究复方黄黛片对Solt-Farber原发性肝癌大鼠血管新生作用的影响。方法:将50只SD大鼠随机分为正常组、模型组、复方黄黛片高剂量组、中剂量组及低剂量组,每组10只。采用Solt-Farber二步法对除正常组外各组大鼠进行原发性肝癌造模,高(280 mg/kg)、中(140 mg/kg)及低剂量组(70 mg/kg)大鼠同时灌胃给予相应剂量的复方黄黛片,正常组与模型组则给予等量生理盐水,连续灌胃18周。末次灌胃12 h后取血,分离血清,检测其中肝功能指标水平(ALT、AST及TBIL)。取血完成,取各组大鼠肝脏,平均分为4份,分别进行病理组织学观察,采用免疫荧光法检测HIF-1α、VEGF及VEGFR-2的表达情况,计算其相对表达量并进行4组比较。结果:与模型组[ALT,(163.74±16.45)IU/L;AST,(331.24±31.35)IU/L;TBIL,(86.11±8.51)IU/L]比较,各组大鼠中血清肝功能指标均明显降低,其差异具有统计学意义(P<0.05);各组指标分别为高剂量组[ALT,(71.43±7.83)IU/L;AST,(112.52±12.58)IU/L;TBIL,(34.23±3.23)IU/L],中剂量组[ALT,(105.32±10.13)IU/L;AST,(223.52±36.58)IU/L;TBIL,(42.93±4.02)IU/L],低剂量组[ALT,(122.34±12.11)IU/L;AST,(254.21±25.14)IU/L;TBIL,(51.27±5.26)IU/L]。高剂量组、中剂量组及低剂量组大鼠肝组织均出现不同程度的癌变,癌细胞呈梁状排列,但癌变程度均不及模型组。与模型组(HIF-1α,14.23±1.28;VEGF,11.52±1.10;VEGFR-2,16.34±1.65)比较,各组大鼠肝组织HIF-1α、VEGF及VEGFR-2的阳性表达情况均明显减轻,且相对表达量均明显降低,其差异具有统计学意义(P<0.05);各组指标分别为高剂量组(HIF-1α,3.92±0.29;VEGF,2.87±0.26;VEGFR-2,3.45±0.40)、中剂量组(HIF-1α,6.36±0.65;VEGF,5.34±0.51;VEGFR-2,5.87±0.60)及低剂量组(HIF-1α,8.53±0.81;VEGF,7.76±0.74;VEGFR-2,8.12±0.87)。结论:复方黄黛片用于Solt-Farber原发性肝癌大鼠,可有效改善肝功能,抑制HIF-1α、VEGF及VEGFR-2等血管新生相关蛋白的表达。
Objective To observe the effects of Fufang Huangdai Tablets(FHT)on Solt-Farber primary liver cancer in mice and its influence on the angiogenesis effects.Methods Totally 50 Sprague-Dawley mice were divided into 5 groups,such as control group,model group,high dose group,medium dose group and low dose group.The models were made by Solt-Farber method in the groups except the model group.The mice in high dose group,middle dose group and low dose group were treated by FHT(280g,140 and 70 mg/kg),the treatment continued for 18 weeks.After 12 h of the last treatment,the serum of mice was obtained and the livers were isolated.The levels of ALT,AST and TBIL were detected in the serum and the pathological and histological were also observed in the groups.The fluorescent-immunohistochemistry was performed in the groups to observe the expression of HIF-1α,VEGF and VEGFR-2.Results Compared with model group[ALT,(163.74±16.45)IU/L;AST,(331.24±31.35)IU/L;TBIL,(86.11±8.51)IU/L],the serum liver function indexes of the rats in each group were significantly reduced,and the differences were statistically significant(P<0.05).The indicators of each group were high dose group[ALT,(71.43±7.83)IU/L;AST,(112.52±12.58)IU/L;TBIL,(34.23±3.23)IU/L];medium dose group[ALT,(105.32±10.13)IU/L;AST,(223.52±36.58)IU/L;TBIL,(42.93±4.02)IU/L],and low dose group[ALT,(122.34±12.11)IU/L;AST,(254.21±25.14)IU/L;TBIL,(51.27±5.26)IU/L].Compared with the model group,the liver pathological histology showed that the canceration degrees were significantly promoted.Compared with model group(HIF-1α,14.23±1.28;VEGF,11.52±1.10;VEGFR-2,16.34±1.65);the positive expression of HIF-1α,VEGF and VEGFR-2 in liver tissues of rats in each group were significantly reduced and the relative expression was significantly decreased,with statistically significant differences(P<0.05).The indicators of each group were high dose group(HIF-1α,3.92±0.29;VEGF,2.87±0.26;VEGFR-2,3.45±0.40),medium dose group(HIF-1α,6.36±0.65;VEGF,5.34±0.51;VEGFR-2,5.87±0.60)and low dose groups(HIF-1α,8.53±0.81;VEGF,7.76±0.74;VEGFR-2,8.12±0.87).Conclusion FHT on Solt-Farber method induced primary liver cancer in mice has a good protective effect,and could inhibit the expression of HIF-1α,VEGF and VEGFR-2.
作者
遆振宇
高小鹏
千东维
慕喜喜
TI Zhen-yu;GAO Xiao-peng;QIAN Dong-wei(Second Department of General Surgery,Third Hospital of Xi'an,Xi'an(710018),China)
出处
《中国中西医结合外科杂志》
CAS
2019年第6期876-881,共6页
Chinese Journal of Surgery of Integrated Traditional and Western Medicine
基金
陕西省重点研发计划（2017SF-039）
