紫檀芪对急性梗阻性胆管炎引起肝损伤的保护作用和机制研究  

Protective effect and mechanism of pterostilbene on liver injury caused by acute obstructive cholangitis

作　　者：王亚利 余建华[1] 沈志宏[1] 朱志杨[1] 鲁葆春[1] WANG Yali;YU Jianhua;SHEN Zhihong(Department of Hepatobiliary and Pancreatic Surgery,Shaoxing Hospital of Zhejiang University,Shaoxing 312000,China.)

机构地区：[1]浙江大学绍兴医院肝胆胰外科,浙江绍兴312000

出　　处：《全科医学临床与教育》2020年第2期109-112,F0002,共5页Clinical Education of General Practice

基　　金：浙江省自然科学基金一般项目(LY19H160016);浙江省医药卫生科技项目(2019ZD057,2020RC127,2020KY978,2018RC077,2018KY836)。

摘　　要：目的探讨紫檀芪对急性梗阻性胆管炎(AOC)引起的肝损伤的保护作用及其可能的机制。方法选用雄性C57BL/6小鼠24只,随机分为假手术组(Sham组)、AOC组、AOC+低剂量紫檀芪组(紫檀芪10 mg·kg^-1·d^-1)和AOC+高剂量紫檀芪组(紫檀芪20 mg·kg^-1·d^-1),每组6只。结扎胆总管3 d后腹腔注射大肠杆菌内毒素建立AOC模型,6 h后检测小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)水平;Western blot法检测肝组织中核因子-κB(NF-κB)的表达水平;取肝组织切片进行苏木精-伊红染色,光镜下观察肝组织损伤情况。结果 AOC组中ALT、AST、TBIL、IL-1β和TNF-α的水平均较Sham组明显升高(q分别=23.29、17.59、25.75、32.28、23.29,P均<0.05),相比于AOC组,AOC+低剂量紫檀芪组和AOC+高剂量紫檀芪组的ALT、AST、TBIL、TNF-α和IL-1β的水平都明显降低(q分别=11.87、8.13、9.51、17.17、11.87;13.68、10.20、13.94、24.28、13.68,P均<0.05)。与AOC+低剂量紫檀芪组比较,AOC+高剂量紫檀芪组TBIL、TNF-α含量明显降低(q分别=4.42、7.10,P均<0.05),而ALT、AST、IL-1β未见明显差异(q分别=1.81、2.07、1.81,P均>0.05)。紫檀芪治疗组肝组织病理损伤也较AOC组明显减轻,另外紫檀芪可以抑制AOC导致的肝组织中p-NF-κB、NF-κB的表达,且与AOC+低剂量紫檀芪组相比,AOC+高剂量紫檀芪组p-NF-κB表达下降,而NF-κB未见明显降低。结论紫檀芪治疗AOC小鼠疗效显著,可改善AOC小鼠肝组织损伤情况,其肝组织病理损伤程度及炎症因子TNF-α的表达水平呈现明显的相关性,其机制可能与抑制肝组织NF-κB通路的激活有关。Objective To explore the protective effect of pterostilbene on liver injury induced by acute obstructive cholangitis(AOC)and its possible mechanism. Methods Totally 24 male C57 BL/6 mice were randomly divided into four groups:sham operation group(Sham group),acute obstructive cholangitis group(AOC group),AOC+low-dose pterostilbene(10 mg·kg^-1·d^-1) group and AOC+ high-dose pterostilbene(20 mg·kg^-1·d^-1)group.AOC model was established by intraperitoneal injection of LPS after ligation of common bile duct for three days.Six hours later,the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected.The expression of nuclear factor-kappa B(NF-κ B)in liver tissue was detected by Western blot method,and the liver tissue sections were stained with hematoxylin and eosin(HE),and the injury of liver tissue was observed under light microscope. Results The levels of ALT,AST,TBIL,IL-1β and TNF-α were significantly increased in AOC group compared with those in Sham group(q=23.29,17.59,25.75,32.28,23.29,P<0.05),and these parameters were significantly decreased after dealing with pterostilbene of different concentration(q=11.87,8.13,9.51,17.17,11.87;13.68,10.20,13.94,24.28,13.68,P<0.05).The levels of TBIL and TNF-α in the AOC+highdose pterostilbene group were significantly lower than those in the AOC + low-dose pterostilbene group(q=4.42,7.10,P<0.05),but there was no significant difference in ALT,AST and IL-1β(q=1.81,2.07,1.81,P>0.05).The pathological injury of liver tissue was also significantly alleviated compared with the AOC group.In addition,pterostilbene could inhibit the expression of p-NF-κB and NF-κB in liver tissue induced by AOC.Compared with the AOC+ low-dose pterostilbene group,the AOC+high-dose pterostilbene group showed a decreasing in the expression of p-NF-κB,while NF-κB did not significantly decrease.Conclusion Pterostilbene is effective in the treatment of AOC mice,it can improve the

关 键 词：紫檀芪 急性梗阻性胆管炎 肝损伤 核因子-ΚB 

分 类 号：R285.5[医药卫生—中药学]