松果菊苷对雨蛙素诱导的急性胰腺炎大鼠模型胰腺及肝损伤的影响与机制  

Effect of echinacoside intervention on liver and pancreas injury in rats with acute pancreatitis and its mechanism

作　　者：马明和 达哇卓玛 刘川川[1,2,3] 樊海宁 MA Minghe;DAWA Zhuoma;LIU Chuanchuan;FAN Haining(School of Clinical Medicine,Qinghai University,Xining 810001,China;Hepatopancreatobiliary Surgery,The Affiliated Hospital of Qinghai University,Xining 810001,China;Qinghai Province Key Laboratory of Hydatid Disease Research,Xining 810001,China)

机构地区：[1]青海大学临床医学院,西宁810001 [2]青海大学附属医院肝胆胰外科,西宁810001 [3]青海省包虫病研究重点实验室,西宁810001

出　　处：《临床肝胆病杂志》2024年第4期782-790,共9页Journal of Clinical Hepatology

基　　金：青海省“昆仑英才·高端创新创业人才计划项目”。

摘　　要：目的通过建立急性胰腺炎(AP)大鼠模型,研究松果菊苷(ECH)对雨蛙素诱导的AP大鼠模型胰腺及肝损伤的改善作用及机制。方法24只SD大鼠随机分为空白组(Con组)、对照组(Con+ECH组)、AP组和AP+ECH组4组,每组各6只。AP模型构建前7 d给予10 mg/kg ECH腹腔注射,雨蛙素末次给药24 h后,腹主动脉取血,分离血清行ALT、AST、乳酸脱氢酶(LDH)、GGT、ALP、Alb、TBil、胆碱酯酶(ChE)、血淀粉酶(Amy)、脂肪酶(LPS)等生化检测;HE染色检测胰腺和肝组织病理学改变;透射电镜观察胰腺和肝组织微观结构改变;ELISA检测肝组织匀浆中IL-1β、IL-6、TNF-α、IL-10水平;免疫组化分析胰腺和肝组织中TNF-α和p-p65 NF-κB水平;Western Blot检测肝组织中NF-κB通路蛋白表达水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用SNK-q或Dunnett’s T3检验。结果与Con组相比,AP组大鼠ALT、AST、GGT、LDH、ALP、TBil、AMY、LPS指标均明显增高(P值均<0.01);肝组织匀浆液IL-1β、IL-6、IL-10、TNF-α水平均增加(P值均<0.01)。ECH干预降低AP大鼠ALT、AST、GGT、LDH、ALP、TBil、AMY、LPS水平,并能抑制IL-1β、IL-6、TNF-α的分泌。HE染色观察可见ECH干预后胰腺组织中腺泡细胞空泡变性和炎性细胞浸润较AP组减轻,肝细胞坏死较AP组减轻。透射电镜检查镜下见ECH干预后肝和胰腺细胞内线粒体肿胀程度较AP组减轻。ECH干预后能部分逆转AP大鼠胰腺和肝组织中p-p65 NF-κB、TNF-α的表达增加。此外,AP大鼠肝组织中MyD88、p-IκBα、p-IKKα、p-p65表达上调,而ECH干预后能部分逆转。结论松果菊苷可通过抑制TLR4/MyD88/NF-κB途径来改善AP诱发的胰腺和肝损伤。Objective To investigate the effect and mechanism of echinacoside(ECH)in improving liver injury in rats with acute pancreatitis by establishing a rat model of acute pancreatitis and liver injury.Methods A total of 24 Sprague-Dawley rats were randomly divided into blank group(Con group),control group(Con+ECH group),acute pancreatitis group(AP group),and acute pancreatitis+ECH intervention(AP+ECH group).The rats were given intraperitoneal injection of 10 mg/kg ECH on day 7 before the establishment of the model of acute pancreatitis;at 24 hours after the last administration of cerulein,blood samples were collected via the abdominal aorta,and serum was separated for biochemical analysis including alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),gamma-glutamyl transpeptidase(GGT),alkaline phosphatase(ALP),albumin(Alb),total bilirubin(TBil),cholinesterase,blood amylase(Amy),and lipase(LPS).HE staining was used to observe the histopathological changes of the pancreas and the liver;transmission electron microscopy(TEM)was used to observe the microstructural changes of pancreas and liver tissue;ELISA was used to measure the levels of interleukin-1β(IL-1β),interleukin-16(IL-6),tumor necrosis factor-α(TNF-α),and interleukin-10(IL-10)in liver tissue homogenate;immunohistochemistry was used to measure the levels of TNF-αand p-p65 NF-κB in pancreas and liver tissue;Western blot was used to measure the expression levels of NF-κB pathway proteins in liver tissue.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the SNK test or the Dunnett’s T3 method was used for further comparison between two groups.Results Compared with the Con group,the AP group had significant increases in ALT,AST,GGT,LDH,ALP,TBil,Amy,and LPS(all P<0.01),as well as significant increases in the levels of IL-1β,IL-6,IL-10,and TNF-αin liver tissue homogenate(all P<0.01).ECH intervention reduced the levels of ALT,AST,GGT,LDH,ALP,TBil,AMY,and LPS and inhibited t

关 键 词：松果菊苷 胰腺炎 大鼠 Sprague-Dawley NF-κB 

分 类 号：R285.5[医药卫生—中药学]