[1]赵佩然,赵玉强,李安琪,等.四逆散对代谢相关脂肪性肝病微循环障碍的影响及机制研究[J].陕西中医,2024,(10):1299-1304.[doi:DOI:10.3969/j.issn.1000-7369.2024.10.001]
　ZHAO Peiran,ZHAO Yuqiang,LI Anqi,et al.Study on the effect and mechanism of Sini powder on the microcirculation disturbance of metabolic associated fatty liver disease[J].,2024,(10):1299-1304.[doi:DOI:10.3969/j.issn.1000-7369.2024.10.001]
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四逆散对代谢相关脂肪性肝病微循环障碍的影响及机制研究
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2024年10期
页码:
1299-1304
栏目:
基础研究
出版日期:
2024-10-05

文章信息/Info

Title:
Study on the effect and mechanism of Sini powder on the microcirculation disturbance of metabolic associated fatty liver disease
作者:
赵佩然1; 赵玉强1; 李安琪1; 王 锐2; 杨 婧1
(1.黑龙江中医药大学基础医学院,黑龙江 哈尔滨 150040; 2.黑龙江中医药大学药学院,黑龙江 哈尔滨 150040)
Author(s):
ZHAO Peiran; ZHAO Yuqiang; LI Anqi; WANG Rui; YANG Jing
(Basic Medical College of Heilongjiang University of Chinese Medicine,Harbin 150040,China)
关键词:
脂肪性肝病;  四逆散;  微循环障碍;  细胞间黏附分子-1;  血管内皮细胞黏附分子-1;  血管内皮生长因子
Keywords:
Fatty liver disease;  Sini powder;  Microcirculation disturbance;  Intercellular cell adhesion molecule-1;  Vascular cell adhesion molecule-1;  Vascular endothelial growth factor
分类号:
R 575.5
DOI:
DOI:10.3969/j.issn.1000-7369.2024.10.001
文献标志码:
A
摘要:
目的:探讨四逆散对代谢相关脂肪性肝病(MAFLD)微循环障碍的影响及作用机制。 方法:将40只SD大鼠分为正常对照组10只和模型组30只,采用蛋氨酸和胆碱缺乏(MCD)饮食建立MAFLD模型。在造模成功之后,将模型组大鼠按照随机原则分为三组,分别为模型组、四逆散治疗组和水飞蓟素阳性药组,之后对正常对照组和模型组给予等体积0.9%氯化钠溶液灌胃,对四逆散治疗组和水飞蓟素阳性药组进行对应药物干预,连续灌胃4周后取材。分别对谷丙转氨酶(ALT)、谷草转氨酶(AST)等肝功能指标、超氧化物歧化酶(SOD)、丙二醛(MDA)等肝脏指标、内皮素1(ET-1)、一氧化氮(NO)等血清指标进行检测,HE染色和Masson染色观察大鼠肝脏组织病理学表现,超声造影观测肝脏微血管血液流速和状态,检测肠系膜微循环指标(微血流速度、微动静脉管径测量)和血液流变学指标(全血黏度、血浆黏度值变化、红细胞压积、红细胞流变学变化)。Western blot法检测肝脏组织细胞间黏附分子-1(ICAM-1)、血管内皮细胞黏附分子-1(VCAM-1)和血管内皮生长因子(VEGF)蛋白表达。 结果:与正常对照组相比,模型组大鼠血清中ALT、AST、ET-1、SOD水平显著提高,NO水平有所下降,MDA水平明显降低(P<0.05),造影剂到达肝动脉时间(HAAT)、造影剂到达肝静脉时间(HVAT)均有不同程度缩短(P<0.01),达峰时间(TP)提前,灌注参数峰值强度(PI)表现减弱,蛋白表达增加(均P<0.01)。与模型组比较,四逆散治疗组大鼠血清ALT、AST、ET-1水平有所下降(P<0.01),NO、SOD、MDA水平接近正常对照组(P<0.01),HAAT、HVAT有上升趋势(P<0.01),TP出现时间延长,PI表现增强(均P<0.01),蛋白表达水平降低。结论:四逆散可在一定程度上改善MAFLD的微循环障碍,其机制可能与抑制VCAM-1、ICAM-1和VEGF蛋白表达以降低血液黏稠度,从而改善血液淤滞情况有关。
Abstract:
Objective:To study the effect and mechanism of Sini powder on the microcirculation disturbance of metabolic associated fatty liver disease(MAFLD).Methods:A total of 40 SD rats were randomized divide into two groups,with 10 rats in the control group and 30 rats in the model group.The model group were induced MAFLD by methionine choline deficient(MCD)diet.After successfully establishing the models,the rats were randomly divided into Chinese herbal medicine group,positive drug group and model group of 8 each.The Chinese herbal medicine group was given Sini powder solution.The positive drug group was given the Silymarin powder suspension.The control group and the model group were given an equal volume of sodium chloride aqueous solution.Four weeks later,the rats were given anesthetic death for sampling.The pathological changes of liver in each group were observed by HE and Masson staining.The blood was collected to detect the liver function indicators [alanine aminotransferase(ALT),aspartate aminotransferase(AST)],liver biochemical indicators [superoxide dismutase(SOD),malondialdehyde(MDA)],serum index [endothelin-1(ET-1),nitrous oxide(NO),contrast-enhanced ultrasound imaging was used to observe the blood flow rate and status of liver microvessels,mesenteric microcirculation indexes were detected(blood flow velocity arteriolar,blood flow velocity venules,arteriolar diameter,venule diameter)and hemorheology indexes(whole blood viscosity,plasmic viscosity,hematocrit,red blood cell rheology).Protein expression in liver tissues were detected by Western blot method [intercellular cell adhesion molecule-1(ICAM-1)、vascular cell adhesion molecule-1(VCAM-1)and vascular endothelial growth factor(VEGF)].Results:Compared with the control group,the serum levels of ALT,AST,ET-1 and SOD in the model group rats were significantly increased(P<0.01),NO and MDA levels were slightly decreased(P<0.05),HAAT and HVAT were shortened to varying degrees(P<0.01),TP appeared earlier,PI performance was weakened(P<0.01),and protein expression increased.Compared with the model group,the serum ALT,AST and ET-1 levels of the traditional Chinese medicine group rats decreased(P<0.01),NO and SOD with MDA levels were close to the control group,HAAT and HVAT showed an upward trend(P<0.01),TP appeared longer,PI expression increased(P<0.01),and protein expression levels decreased.Conclusion:Sini powder can improve microcirculation disorders of MAFLD to a certain extent,and its mechanism may be related to inhibiting the expression of VCAM-1,ICAM-1 and VEGF proteins,reducing blood viscosity,and thus clearing blood stasis.

参考文献/References:

[1] 范建高.代谢相关脂肪性肝病现已成为我国第一大慢性肝病[J].中华医学信息导报,2021,36(6):6.
[2] GRACIA S J,MARRONE G,FERNANDEZ I A.Hepatic microcirculation and mechanisms of portal hypertension[J].Nat Rev Gastroenterol Hepatol,2019,16(4):221-234.
[3] 刘定,潘富珍,杨沈秋,等.肝脾肾同治法重塑自噬稳态抗肝纤维化的理论探讨[J].现代中西医结合杂志,2022,31(11):1521-1525.
[4] DAVIES T,WYTHE S,O'BEIRNE J,et al.Review article:The role of the microcirculation in liver cirrhosis[J].Aliment Pharmacol Ther,2017,46(9):825-835.
[5] 李安琪,赵玉强,赵佩然,等.代谢相关脂肪性肝病微循环障碍与微血管系统的相关性[J].临床肝胆病杂志,2023,39(8):1939-1945.
[6] 李紫健,牛建海,刘文英,等.基于“血气不和,百病乃变化而生”理论运用通法治疗脂肪肝[J].陕西中医,2022,43(10):1436-1438,1441.
[7] MU J,CHENG F,WANG Q,et al.Sini powder ameliorates the inflammatory response in rats with stress-induced non-alcoholic fatty liver disease by inhibiting the nuclear factor kappa-B/pyrin domain-containing protein 3 pathway[J].J Tradit Chin Med,2020,40(2):253-266.
[8] SHU Z,HE W,SHAHEN M,et al.Clarifying of the potential mechanism of Sinisan formula for treatment of chronic hepatitis by systems pharmacology method[J].Biomed Pharmacother,2018,100:532-550.
[9] 冯贺龙,王晓雪,张福利.基于网络药理学的四逆散保肝作用机制研究[J].中草药,2020,51(24):6258-6268.
[10] 岳悦,郑桂玲,褚月颉,等.四逆散合平胃散联合罗格列酮治疗代谢综合征疗效及对患者氧自由基水平的影响[J].陕西中医,2022,43(4):479-482.
[11] 张声生,李军祥.非酒精性脂肪性肝病中医诊疗专家共识意见(2017)[J].临床肝胆病杂志,2017,33(12):2270-2274.
[12] 赛俊婷,张唤唤,康钦扬,等.童光东教授治疗肝癖临床经验[J].中西医结合肝病杂志,2024,34(2):178-181.
[13] 曹兴旺,杨露银,江花,等.“络玄府”理论初探[J].四川中医,2023,41(12):51-55.
[14] 田晶,张向玉,段晓龙,等.《黄帝内经》血理论及研究[J].光明中医,2024,39(4):670-673.
[15] 施敏,赵会芳.中医肝病瘀血与肝脏微循环障碍[J].湖北中医杂志,1993,27(5):28-29.
[16] 何浩强,陈光,高嘉良,等.气滞血瘀证生物学基础研究进展[J].中华中医药杂志,2019,34(9):4167-4171.
[17] 李毅,胡娜,胡兰贵.四逆散药理作用及治疗内科疾病的临床应用研究[J].辽宁中医杂志,2024,51(4):6-10.
[18] NOGUCHI N, TERAMOTO K, OCHIAI T, et al.The close participation of ET-1 and NO in human hepatic hemodynamics[J].Hepatol Res,2006,36(2):86-93.
[19] XU Y,LI S.Blockade of ICAM-1:A novel way of vasculitis treatment[J].Biochem Biophys Res Commun,2009,381(4):459-461.
[20] TRONCOSO M F,ORTIZ-QUINTERO J,GARRIDO-MORENO V,et al.VCAM-1 as a predictor biomarker in cardiovascular disease[J].Biochim Biophys Acta Mol Basis Dis,2021,1867(9):166170.
[21] SINGH V,KAUR R,KUMARI P,et al.ICAM-1 and VCAM-1:Gatekeepers in various inflammatory and cardiovascular disorders[J].Clin Chim Acta,2023,548:117487.
[22] MELINCOVICI C S,BOSCA A B,SUSMAN S,et al.Vascular endothelial growth factor(VEGF)-key factor in normal and pathological angiogenesis[J].Rom J Morphol Embryol,2018,59(2):455-467.
[23] 龚珂,唐莉,孙文涛,等.人血管内皮抑素对糖尿病大鼠视网膜病变的干预效果及对VCAM-1、ICAM-1以及VEGF等蛋白表达的影响[J].临床和实验医学杂志,2021,20(11):1143-1147.
[24] 张伟,王玉琴,李锋,等.二苯乙烯苷预防性干预大鼠动脉硬化对其ICAM-1、VCAM-1及VEGF表达的影响[J].中国药理学通报,2007,23(12):1630-1635.
[25] 顾婷婷,余燕玲,尚莉丽.健脾补肺化痰方对哮喘大鼠血清VCAM-1、ICAM-1、VEGF水平的影响[J].江西中医药大学学报,2017,29(5):62-64,108.

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备注/Memo

备注/Memo:
基金项目:国家自然科学基金青年基金资助项目(81603418,82074271); 黑龙江省自然科学基金资助优秀青年人才项目(2020YQ05)
更新日期/Last Update: 2024-10-08