熊果酸治疗急性胰腺炎大鼠的效果及作用机制  

Preliminary study on the effect of ursolic acid for rats with acute pancreatitis

作　　者：米凯 黄锐[2] 熊伟[2] 许建[2] 伍刚[2] 邓锋 MI Kai;HUANG Rui;XIONG Wei;XU Jian;WU Gang;DENG Feng(The Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu 610051, China;Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu 610072, China)

机构地区：[1]成都医学院第二附属医院·核工业四一六医院,四川成都610051 [2]四川省医学科学院·四川省人民医院,四川成都610072

出　　处：《西部医学》2020年第11期1570-1575,共6页Medical Journal of West China

基　　金：国家自然科学基金(81302161);四川省卫计委科研课题(150215,17PJ587)。

摘　　要：目的探讨熊果酸(UA)对急性胰腺炎(AP)大鼠的治疗作用以及可能的作用机制。方法30只雄性SD大鼠随机分为假手术组(Sham组)、急性胰腺炎组(AP组)和熊果酸组(UA组),每组10只。除假手术组外,其余两组采用逆行胰胆管注射5%牛黄胆酸钠(1 mL/kg)诱导大鼠AP模型,假手术组注射等量生理盐水,造模30 min后,UA组给予熊果酸150 mg/kg灌胃,其余两组灌等体积蒸馏水,灌胃12 h后处死大鼠,收集胰腺和血清。酶联免疫吸附测定法检测大鼠血清中白介素1β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)含量,全自动生化分析仪测定血清中淀粉酶含量,HE和TUNEL染色观察胰腺病理和凋亡情况,蛋白免疫印迹实验检测胰腺Bcl-2、Bax、cleaved-caspase3、p38MAPK、p-p38MAPK表达情况,实时荧光定量PCR检测p38MAPK mRNA表达水平。结果与AP组相比,UA组血清淀粉酶、TNF-α、IL-1β、IL-6水平显著下降(P<0.01),胰腺病理情况好转,凋亡细胞减少,Bax/Bcl-2、p-p38MAPK/p38MAPK比值和cleaved-caspase3表达量显著降低(P<0.01)。结论熊果酸能降低血清炎性因子和淀粉酶水平,改善胰腺病理损伤和凋亡,其作用机制可能与抑制p38MAPK活性有关。Objective To investigate the therapeutic effect of ursolic acid(UA)on acute pancreatitis(AP)rats and its possible mechanism.Methods 30 male SD rats were randomly divided into sham operation group(Sham),acute pancreatitis group(AP)and ursolic acid group(UA).Except the sham operation group,the other groups were treated with retrograde pancreaticobiliary injection of 5%sodium taurocholate(1ml/kg)to induce the AP model,and the sham group was injected with the same amount of normal saline.After modeling for 30 minutes,the UA group was given ursolic acid.150 mg/kg was intragastrically administered,and the other two groups were given equal volume of distilled water.The rats were sacrificed 12 hours after gavage,and the pancreas and serum were collected.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The amylase content in serum was determined by automatic biochemical analyzer.The pathological and apoptotic aspects of pancreas were observed by H&E and TUNEL staining.The expressions of Bcl-2,Bax,cleaved-caspase3,p38MAPK and p-p38MAPK were detected by Western blotting.The expression of p38MAPK mRNA was detected by real-time fluorescent quantitative PCR.Results Compared with the AP group,the levels of amylase,TNF-α,IL-1β,and IL-6 in the UA group were significantly decreased(P<0.01),the pathological condition of the pancreas was improved,and the apoptotic cells were decreased.The Bax/Bcl-2,p-p38MAPK/p38MAPK ratio and cleaved-caspase3 expression were significantly decreased(P<0.01).Conclusion Ursolic acid can reduce the levels of serum inflammatory factors and amylase,improve the pathological damage and apoptosis of pancreas,and reduce acute pancreatitis.The mechanism may be related to the inhibition of p38MAPK activity.

关 键 词：熊果酸 急性胰腺炎 大鼠 P38MAPK 

分 类 号：R576[医药卫生—消化系统]