3-甲基腺嘌呤对重症急性胰腺炎模型大鼠PI3K/AKT信号通路调节和肝细胞保护作用的研究  

Protection and mechanism of 3-methyladenine on liver cells in rats with severe acute pancreatitis through the PI3K/AKT signaling pathway

作　　者：章露尹 陆贝 ZHANG Luyin;LU Bei(Department of Hepatopancreatobiliary Surgery,Affiliated Hangzhou First People's Hospital,Xihu University School of Medicine,Hangzhou,Zhejiang 310006,China)

机构地区：[1]西湖大学医学院附属杭州市第一人民医院肝胆胰外科,杭州310006

出　　处：《浙江中西医结合杂志》2024年第12期1093-1098,共6页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：浙江省医药卫生科技计划项目(No.2023KY921)。

摘　　要：目的探讨3-甲基腺嘌呤(3-MA)对重症急性胰腺炎(SAP)模型大鼠肝细胞的保护作用和调控机制。方法健康雄性清洁级SD大鼠45只,按照随机数字表法分为SAP模型组(L-精氨酸二次腹腔注射法制模)、3-MA组(SAP模型制备后静脉注射3-MA)和假手术组(仅注射生理盐水),每组15只。造模后12、24、48 h处死大鼠取材,每组5只。观察各组大鼠苏木精-伊红染色肝组织病理改变,肝组织磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、核因子-κB(NF-κB)蛋白,肝功能指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST),血清炎症因子白细胞介素(IL)-1β、IL-6等表达情况。结果与假手术组比较,SAP模型组各时间点肝组织病理损伤加重,血清炎症因子、肝功能指标升高(P<0.05),肝组织NF-κB、PI3K、AKT蛋白表达明显上升(P<0.05)。3-MA组造模后12、24、48 h肝组织受损程度较SAP模型组轻,血清ALT[(188.15±9.32)U/L比(211.25±9.24)U/L、(197.25±7.25)U/L比(289.46±8.25)U/L、(263.30±9.14)U/L比(354.68±15.45)U/L]、AST[(279.45±26.35)U/L比(415.30±32.33)U/L、(358.20±53.35)U/L比(627.30±37.51)U/L、(419.40±38.48)U/L比(944.60±40.58)U/L]、IL-1β[(398.34±54.44)ng/L比(715.46±88.26)ng/L、(460.11±61.22)ng/L比(781.54±91.34)ng/L、(481.24±67.41)ng/L比(805.78±95.37)ng/L]、IL-6[(618.50±88.15)ng/L比(975.28±130.25)ng/L、(960.47±125.77)ng/L比(1514.60±189.12)ng/L、(1056.32±136.10)ng/L比(1675.32±182.05)ng/L]水平低于SAP模型组(P<0.05),肝组织NF-κB[(8978.96±234.35)比(31015.52±1225.15)、(16671.05±1385.52)比(54221.05±1542.50)、(23422.83±2118.60)比(71650.72±2315.65)]、PI3K[(598.45±46.35)比(915.50±42.30)、(966.20±52.30)比(1500.30±58.50)、(1380.40±68.40)比(2545.60±70.50)]、AKT[(0.15±0.02)比(0.25±0.04)、(0.25±0.05)比(0.46±0.05)、(0.30±0.04)比(0.68±0.05)]蛋白表达低于SAP模型组(P<0.05)。结论3-MA可能通过PI3K/AKT信号通路调控自噬,从而发挥SAP肝细胞损伤的保护作用。Objective To investigate the protective effect and regulatory mechanism of 3-methyladenine(3-MA)on liver cells in a rat model of severe acute pancreatitis(SAP).Methods Forty-five healthy male clean SD rats were randomly divided into the SAP model group(induced by two injections of L-arginine),the 3-MA group(3-MA administered intravenously after SAP model induction),and the sham operation group(control group injected with normal saline only)according to a random number table,with 15 rats in each group.The rats were sacrificed at 12,24,and 48 h after modeling,and the samples were collected from five rats at each time point per group.The pathological changes in liver tissue were observed using hematoxylin and eosin staining.The expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), nuclear factor-κB (NF-κB) proteins in liver tissue, as well as liver function indicators such as alanine aminotransferase(ALT) and aspartate aminotransferase (AST), were examined. Additionally, serum levels of inflammatory factors such as interleukin(IL)-1β and IL-6 were also examined. Results Compared with the sham operation group, the SAP model group showed aggravated liver histopathological damage, increased serum inflammatory factors, and liver function indicators at all points(P<0.05). The expression levels of NF-κB, PI3K, and AKT proteins in liver tissue were significantly increased(P<0.05). In the 3-MA group, the degree of liver tissue damage was milder than that in the SAP model group at 12, 24, and 48 h after modeling. Compared with the SAP model group, the 3-MA group showed decreased levels of serum ALT [(188.15±9.32) vs. (211.25±9.24) U/L, (197.25±7.25) vs. (289.46±8.25) U/L, (263.30±9.14) vs. (354.68±15.45) U/L], AST [(279.45±26.35) vs. (415.30±32.33) U/L, (358.20±53.35) vs. (627.30±37.51) U/L, (419.40±38.48) vs. (944.60±40.58) U/L], IL-1β [(398.34±54.44) vs. (715.46±88.26) ng/L, (460.11±61.22) vs. (781.54±91.34) ng/L, (481.24±67.41) vs. (805.78±95.37) ng/L], and IL-6 [(618.50

关 键 词：大鼠 重症急性胰腺炎 3-甲基腺嘌呤 自噬 PI3K/AKT信号通路 

分 类 号：R576[医药卫生—消化系统]