热休克蛋白在结肠炎和胰腺炎时的表达特点及大麻类物质WIN和O-1602的影响

Effects of cannabinoids WIN and O-1602 on expression of HSPs in mice with colitis or acute pancreatitis

目的:观察几种热休克蛋白(heat-shock proteins,HSPs)在实验性结肠炎和实验性急性胰腺炎炎症组织中表达的变化,同时研究大麻经典受体1和受体2激动剂WIN55和212-2(WIN),以及新型受体GPR55激动剂O-1602对HSPs表达的影响及可能的意义。方法:用C57/BL小鼠,通过连续饮用7 d 4%葡聚糖硫酸钠(dextran sulfate sodium,DSS)复制结肠炎模型;通过腹腔注射雨蛙肽(cerulein,50μg/kg,每小时1次,连续6次)复制急性胰腺炎模型。同时设各模型组及WIN、O-1602治疗组,检测不同处理组小鼠结肠和胰腺组织形态学改变、血浆促炎细胞因子包括白细胞介素-6(IL-6)及细胞因子诱导的中性粒细胞化学趋化因子-1(cytokine-inducedneutrophil chemoattractant-1,CINC-1)的水平和淀粉酶活性,同时用免疫组化方法检测结肠和胰腺组织HSPs(HSP27、HSP60、和HSP70)的表达特点。结果:在DSS诱导的小鼠结肠炎及cerulein诱导的小鼠胰腺炎模型,其结肠和胰腺组织分别出现典型的炎症及损伤,血浆促炎因子水平升高(P<0.05),在胰腺炎小鼠还有血浆胰淀粉酶活性的升高。在结肠炎症组织,HSP27表达明显升高,HSP60和HSP70表达降低;WIN具有一定的抗炎作用,并能显著提高结肠炎结肠组织HSP27和HSP70的表达(P<0.05)。在急性胰腺炎的胰腺组织,HSP27和HSP70表达升高,HSP60表达有所降低;O-1602有一定的抗炎作用,也能提高HSP70的表达,但总体来看,对这3种HSPs的影响均不太明显(P>0.05)。结论:DSS和cerulein分别诱导小鼠结肠炎和急性胰腺炎的发生;在这2种模型的炎症组织中HSPs的表达变化不一。大麻类物质WIN和O-1602均有一定的抗炎作用,也在一定程度上提高部分HSPs的表达。HSPs的高表达是否与大麻类物质的抗炎作用有关值得进一步的研究。

AIM： To investigate the effects of cannabinoids WIN55,212-2（WIN） and O-1602 on the expression of heat-shock proteins（HSPs）,such as HSP27,HSP60 and HSP70,in the inflammatory tissues of mice with experimental colitis or acute pancreatitis（AP）.METHODS： Mouse colitis was induced by feeding the C57/BL with 4% dextran sulfate sodium（DSS） for 7 d,and AP was induced by intraperitoneal injection of ceruline in the mice（50 μg/kg hourly,with a total of 6 times）.The mice were intraperitoneally administered with WIN or O-1602 for the therapeutic evaluation by observing the following parameters： pathological changes of the tissues,plasma activity of amylase,plasma levels of IL-6 and cytokine-induced neutrophil chemoattractant-1（CINC-1）,and HSP expression in the colonic and pancreatic tissues.RESULTS： Compared with normal control mice,the colonic tissues from colitis mice and the pancreatic tissues from AP mice appeared obvious signs of inflammation and injury.The plasma levels of IL-6 and CINC-1 significantly increased in colitis mice and AP mice.In DSS group of colitis mice,HSP27 expression increased,but HSP60 and HSP70 were reduced in the colonic tissues.WIN showed anti-inflammatory effects on the pathological changes of colonic tissues and the plasma cytokine levels.WIN also improved the expression of HSP70（P0.05）.In AP group,the expression of HSP27 and HSP70 in pancreatic tissues increased,and HSP60 decreased.O-1602 also showed some anti-inflammatory effects on the changes of the pathological tissues and the plasma parameters,but had no obvious effects on the HSP expression（P0.05）.CONCLUSION： The experimental colitis and acute pancreatitis in mice were induced by feeding DSS and injection of cerulein,respectively.The changes of HSP expression were different in the inflammatory tissues.WIN and O-1602 show anti-inflammatory effects and increase the expression of several HSPs to some extent.