沙棘原花青素对应激性胃溃疡大鼠上皮细胞凋亡与增殖的影响

目的探讨沙棘原花青素对应激性胃溃疡大鼠上皮细胞凋亡与增殖的影响及其可能的机制。方法60只♂W ist-ar大鼠随机分为6组:正常组,对照组,低、中、高剂量组及雷尼替丁阳性对照组。采用束缚-浸水应激的方式造应激性胃溃疡模型,造模前灌胃不同剂量的SBPC或阳性药物。测定溃疡指数、大鼠血浆EGF及NO的水平;大鼠血浆NOS及iNOS的活性;免疫组化的方法测定胃粘膜组织中iNOS、EG-FR及PCNA的表达;采用原位末端标记法检测胃粘膜上皮细胞的凋亡。结果与对照组相比,高剂量组SBPC(150 mg.kg-1)的溃疡指数明显降低(P<0.01);血浆EGF的水平升高(P<0.05),血浆NO的浓度(P<0.01)降低;NOS及iNOS的活力降低(P<0.05);粘膜中的iNOS的表达降低(P<0.01),EGFR的表达增强((P<0.01),PCNA的表达增强(P<0.05),凋亡指数降低(P<0.05)。结论SBPC可能通过调节EGF和NO促进大鼠的细胞增殖抑制细胞凋亡,从而对应激性胃溃疡的发生起保护作用。

Effects of sea buckthorn procyanidins on apoptosis and proliferation of gastric epithelium mucosae in gastric ulcer of rats induced by water-immersion restraint stress

Aim The effects of different Sea Buckthorn Procyanidins(SBPC)on apoptosis and proliferation of gastric epithelium mucosae in gastric ulcer which induced by restraint water-immerse were studied.Method 60 Wistar male rats were assigned into 6 groups at random: normal(unstressed),control,low-dose(SBPC 50 mg·Kg~(-1) diet) supplement,medium-dose(SBPC 100 mg·Kg~(-1) diet) supplement,high-dose(SBPC 150 mg·Kg~(-1) diet) supplement and ranitidine hydrochloride 30 mg·Kg~(-1) diet supplement.Water immersion and restraint stress(WRS)induced gastric injury was used as the experimental model of acute gastric ulcer.Rats were orally administrated with SBPC/ranitididine/water before stressed.Ulcer index(UI)was measured;the level of epidermal growth factor(EGF)and the activity of NOS and iNOS in plasma were determined;the expression of epidermal growth factor receptor(EGFR),iNOS and proliferating cell nuclear antigen(PCNA)around ulcer were detected by immunohistochemical method.The apoptotic cells in the gastric mucosa were examined through the methods of terminal deoxynucleatidyl transferase mediated DUTP nick and labeling(TUNEL).Results Compared with the control group,UI was significantly decreased(P<0.01),In plasma,the EGF level was dose dependently increased,NO level and NOS,iNOS activity were all dose dependently decreased by SBPC.In gastric mucosae,the expression of EGFR protein and the PCNA were increased significantly(P<0.01,P<0.05,respectively),meanwhile the apoptosis index(AI)was significantly decreased(P<0.05).Conclusion SBPC inhibited the ulcer formation induced by high stressed stimulation through the regulation between apoptosis and proliferation in gastric epithelium mucosae.