目的:观察2种新型大麻类制剂O-1602和大麻二酚(CBD)对雨蛙肽(CAE)诱导的小鼠急性胰腺炎(AP)的抗炎作用,并通过其对热休克蛋白60(HSP60)表达的影响,探讨其可能的机制.方法:以CAE腹腔注射(50μg·kg-1·h-1,共6次)复制小鼠AP模型,对照组用生理盐水(NS)替代CAE;给AP小鼠腹腔注射O-1602或CBD作为治疗组.组织学检查评估不同处理组胰腺组织形态学改变;测定血浆淀粉酶及脂肪酶活性(生化法)、血浆细胞因子如肿瘤坏死因子α(TNF-α)及白细胞介素6(IL-6)的水平(ELISA法),以及肺脏中髓过氧化物酶(MPO)活性的变化(生化法);同时,用 real-time PCR和Western blotting测定胰腺组织热休克蛋白(HSP60) mRNA和蛋白的表达特点.结果:AP组小鼠胰腺组织出现明显损伤及炎症表现;此类表现在AP+O-1602及AP+CBD治疗组得到明显改善.AP组血浆淀粉酶及脂肪酶活性、TNF-α及IL-6水平、肺脏MPO水平较NS组均有显著升高(P＜0.05);而在AP+O-1602及AP+CBD组,这些指标均较AP组明显降低(P＜0.05).同时,胰腺组织HSP60 mRNA和蛋白的表达量在AP组均降低(P＜0.05),O-1602或CBD处理可一定程度提高HSP60的表达(P＜0.05).结论:CAE可成功诱导小鼠AP的发生,并伴有一定程度的全身炎症反应,O-1602和CBD可改善胰腺局部损伤程度及全身炎症程度,其机制可能与大麻类物质对炎症介质、细胞因子的抑制以及提高细胞保护因子HSP60的表达有关.%AIM : To investigate the therapeutic effects of O - 1602 and cannabidiol ( CBD ), the new kinds of cannahis preparations, on caerulein ( CAE ) - induced acute pancreatitis ( AP ) in mice.METHODS : AP was induced by intraperitoneal injection ( ip ) of CAE in mice ( 50 μg/kg hourly with a total of 6 times), and the mice in control group were given normal saline ( NS ) ip in stead of CAE in the same way.The AP mice were administrated O - 1602 or CBD for the therapeutic evaluation by observing the following parameters : pathological changes of pancreatic tissue, plasma activity of amylase and lipase ( biochemical methods ) , the levels of TNF - α and IL - 6 in the plasma ( ELISA ) , and the activity of myeloperoxidase ( MPO ) in the lung ( biochemical methods ).Meanwhile, real - time PCR and Western blotting were used to evaluate the expression of heat shock protein 60 ( HSP60 ) at mRNA and protein levels, respectively.RESULTS : The pancreatic tissues in AP group appeared obvious edema and neutrophil infiltration, which were significantly improved by treating with AP + O - 1602 or AP + CBD.The activity of amylase , lipase and MPO, as well as the levels of TNF - α and IL - 6 in AP group significantly increased compared with NS group ( P ＜ 0.05 ), while these parameters were significantly lower in AP + O - 1602 group and AP + CBD group than those in AP group.Meanwhile, the expression of HSP60 at mRNA and protein levels in pancreas tissues was reduced in AP group ( P ＜ 0.05 ), and was improved to some extent after treating with O - 1602 or CBD ( P ＜0.05 ).CONCLUSION : The O - 1602 and CBD show anti - inflammatory effects on CAE induced AP in mice and the mechanisms might be related to the effects of cannabinoids on inhibiting inflammatory mediators and cytokines, and increasing the expression of cytoprotective factor HSP60.
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