摘要
目的探讨HIF-1α、VEGFA在沙鼠肝泡状棘球蚴组织的表达及血管生成过程中的作用。方法126只沙鼠随机分成空白组(6只)、假手术组(60只)、模型组(60只),采用开腹直视肝脏穿刺法建立泡状棘球蚴动物模型,假手术组接种同体积的PBS,术后第3d、7d、14d、28d、42d、56d、70d、84d、98d、112d随机取6只沙鼠,取临近病变的边缘区组织及正常肝组织。采用HE观察病理改变;qRT-PCR、原位杂交、免疫组化检测HIF-1α、VEGFA表达,CD34标记微血管进行MVD计数。结果HE染色根据病理特点将病程分为早期(14d内)、中期(14d^56d)、晚期(56d后)。模型组泡状棘球蚴组织随感染时间不同,其HIF-1αmRNA随感染时间呈动态改变,术后第14d其表达量高于空白组、低于假手术组(F=82.732,P<0.001);术后第42d、112d其相对表达量均高于空白组与假手术组(χ^2=11.536,χ^2=15.189,P<0.01);模型组术后第14dVEGFAmRNA相对表达量低于空白组及假手术组(χ^2=15.174,P<0.01);术后第42d、112d,VEGFAmRNA表达量均高于空白组与假手术组(χ^2=15.158,χ^2=15.158,P<0.01)。模型组术后第14d、42d、112dHIF-1α表达均高于空白组、假手术组(χ^2=8.627,χ^2=9.000,F=15.690,P<0.01);模型组术后第14d、42dVEGFA表达高于空白组、假手术组(F=11.250,F=70.059,P<0.001);模型组术后第14d、42d、112d,其MVD-CD34均高于空白组、假手术组(χ^2=12.517,P<0.01,χ^2=13.157,P<0.01;χ^2=13.220,P<0.01)。结论沙鼠感染肝泡状棘球蚴中期,病变边缘区HIF-1α、VEGFA表达均升高,同时伴有大量微血管生成,可能存在HIF-1α转录因子激活并上调VEGFA的表达,促进肝泡状棘球蚴组织边缘区的血管新生。
The aims of our study is to investigate the role of HIF-1α and VEGFA in the expression and angiogenesis of hepatic vesicular echinococcosis tissue. A total of 126 gerbils were randomly divided into blank group (6 rats), sham operation group (60 rats) and model group (60 rats). The model group was established with E. multilocularis suspension through abdominal opening injection in liver. The rats were inoculated with the same volume of PBS. Six gerbils were randomly selected on the 3rd, 7th, 14th, 28th, 42nd, 56th, 70th, 84th, and 98th day, and the marginal tissues and normal liver tissues of adjacent lesions were taken. Pathological changes were observed by HE;qRT-PCR, in situ hybridization and immunohistochemistry were used to detect the expression of HIF-1α and VEGFA, and CD34 labeled microvessels were used for MVD counting. Results showed that HE staining was divided into early stage (14 days), medium stage (14-56 days) and late stage (56 days later) according to pathological features. The HIF-1α mRNA of the model group was increased with the infection time. The expression of HIF-1α mRNA was higher than that of the blank group and the sham operation group ( F=82.732, P <0.001) on the 14th day. The relative expression of the HIF-1α mRNA was higher than that of the blank group and the sham operation group (χ^2=11.536,χ^2=15.189, P <0.01) on the 42nd and 112th day. The expression level of VEGFA mRNA was lower than that of the blank group and the sham operation group (χ^2=15.174, P <0.01) on the 14th day, and model group was higher than that in the blank group and the sham operation group on the 42nd and 112th days after operation(χ^2=15.158,χ^2=15.158, P <0.01). The expression of HIF-1α in the model group was higher than that in the blank group and sham operation group on the 14th, 42nd and 112th day (χ^2=8.627,χ^2=9.000, F=15.690,P <0.01). The expression of VEGFA in the model group was higher than that in the blank group and the sham operation group ( F=11.250;F=70.059, P <0.001). The model group was on the 14th, 42nd and 112th day. MVD-CD34 was higher than the blank group and sham operation group (χ^2=12.517, P<0.01,χ^2=13.157, P<0.01;χ^2=13.220, P <0.01). In conclusion, in the middle stage of hepatic alveolar echinococcosis, the expression of HIF-1α and VEGFA in the marginal zone of the gerbils is increased, accompanied by a large number of microangiogenesis. The activation of HIF-1α transcription factor may be up-regulated and the expression of VEGFA may be up-regulated to promote angiogenesis in the marginal of the echinococcosis tissue.
作者
郭黎姣
姜慧娇
韩欢欢
杨雄峰
周青
王小义
李林林
廖振宇
陈雪玲
吴向未
GUO Li-jiao;JIANG Hui-jiao;HAN Huan-huan;YANG Xiong-feng;ZHOU Qing;WANG Xiao-yi;LI Lin-lin;LIAO Zhen-yu;CHEN Xue-ling;WU Xiang-wei(The First Affiliated Hospital,School of Medical Sciences,Shihezi University,Shihezi 832008,Xinjiang Uygur Autonomous Region,China;Department of Immunology,School of Medicine,Shihezi University,Shihezi,Xinjiang 832008,China)
出处
《中国人兽共患病学报》
CAS
CSCD
北大核心
2019年第7期639-646,共8页
Chinese Journal of Zoonoses
基金
国家自然科学基金(No.81760570)~~
