摘要
目的采用基因组学方法分析幽门结扎致肝功能异常病理机制,并从基因水平探讨连翘-4干预机制。方法取50只大鼠,分为5组,即正常组、模型组、连翘-4(低、中、高剂量)组,通过幽门结扎法引起肝功能异常动物模型,采用基因芯片技术找到差异基因、实时荧光定量链式聚合酶反应(RT-PCR)法检测大鼠肝脏组织中Dhrs3表达变化及测定血清和肝组织中肝损伤相关指标。结果与正常组比较,模型组大鼠背毛耸立、蜷缩、动作缓慢,腹腔内聚集有大量的液体、且腹膜具有明显的黄色、黄尿;血清指标比较,AST、ALT、BILD2、BILT3活性明显增加(P<0.01或P<0.05);形态学观察,肝细胞有明显的脂肪变、水肿、边膜外肝细胞大量坏死、肝细胞具有一定程度的凋亡;基因组学结果,差异基因共1752,其中大部分差异基因与肝脏的新陈代谢有关,即药物代谢、过氧化物酶、胆汁酸、脂肪酸、维生素新陈代谢等;RT-PCR验证结果,模型组对Dhrs3基因下调至0.3949倍。与模型组比较,连翘-4组大鼠外观与腹腔内情况、各种血清指标均明显好转,且有统计学意义;基因组学检测出差异基因共713;RT-PCR结果显示,连翘-4组对Dhrs3基因下调至7.7586倍。结论幽门结扎后“精华与糟粕分解”紊乱导致肝功能异常,并能引起肝组织形态学、肝功能临床敏感指标的异常,从基因组学角度分析,此病理过程代谢功能紊乱并能引起Dhrs3基因失调。本次研究中连翘-4干预结果显示,各种临床指标不仅明显好转且对Dhrs3基因具有调节而改善维生素代谢。
Objective To analyze the pathological mechanism of liver function abnormality caused by pyloric ligation by genomics method and explore the intervention mechanism of Lianqiao-4 from the gene level.Method:Fifty rats were divided into 5 groups,namely the normal group,the model group,the Lianqiao-4 low,middle and high dose groups.The pylorus ligation method was used to cause liver function abnormal animal model,using gene chip technology to find out differences between gene and Real-time fluorescence quantitative chain polymerase reaction(RT-PCR)method to detect Bcat1,Dhrs3 expression changes in liver tissue of rats and the determination of related parameters of liver damage in serum and liver tissue.Results Compared with the normal group and the model group,the rats in the model group had high back hair,curled up,slow movement,a large amount of fluid in the abdominal cavity,and yellow urine and obvious yellow in the peritoneal membrane.Compared with serum indexes,the activities of AST,ALT,BILD2 and BILT3 were significantly increased(P<0.01 or P<0.05).Morphological observation showed that hepatocytes had obvious steatosis,edema,massive necrosis of hepatocytes outside the marginal membrane,and hepatocytes had a certain degree of apoptosis.Genomics results showed that there were 1752 differential genes,most of which were related to liver metabolism,namely drug metabolism,peroxidase,bile acid,fatty acid,vitamin metabolism,etc.RT-PCR results showed that Dhrs3 gene in the model group was down regulated to 0.3949 times.Compared with those of the model group,the appearance,intraperitoneal condition and various serum indexes of Lianqiao-4 groups were significantly improved,and there was statistical significance.A total of 713 differential genes were detected by genomics.RT-PCR showed that the Dhrs3 gene in Lianqiao-4 groups was down regulated to 7.7586 times.Conclusion After pyloric ligation,the disorder of“essence and dregs decomposition”leads to abnormal liver function.It can also cause abnormal liver histology and clinical sensitive indexes of liver function.Analyzing from the perspective of genomics,this pathological process can cause Dhrs3 gene disorder.In this study,the intervention results of Lianqiao-4 showed that various clinical indicators were not only significantly improved,but also adjusting the DHRS3 gene disorders accordingly.
作者
吴圆圆
白塔那
宫菊花
佟山
王欢
WU Yuanyuan;BAI Tana;GONG Juhua;TONG Shan;WANG Huan(Inner Mongolia University for Nationalities,Tongliao 028000,Inner Mongolia,China;Affiliated Hospital of Inner Mongolia University for Nationalities,Tongliao 028000,Inner Mongolia,China;Mongolian Medicine Pharmacology Laboratory,College of Mongolian Medicine,Inner Mongolia University for Nationalities,Tongliao 028000,Inner Mongolia,China;National Medical Products Administration(NMPA)key Laboratory for Quality Control of Traditional Chinese Medicine(Mongolian Medicine),Tongliao 028000,Inner Mongola,China)
出处
《辽宁中医杂志》
CAS
2022年第2期144-148,223-224,共7页
Liaoning Journal of Traditional Chinese Medicine
基金
国家自然科学基金地区科学基金(81760765)
关键词
“精华与糟粕分解”理论
幽门结扎法
肝功能异常
基因组学
连翘-4干预机制
“essence and dregs decomposition”theory
pyloric ligation
abnormal liver function
genomics
Lianqiao-4 intervention mechanism
