替普瑞酮对类固醇性溃疡大鼠胃黏膜热休克蛋白70和c—fos表达的影响  

Effects of teprenone on expression of heat shock protein 70 and c-fos in stomach following prednisolone ingestion： experiment with rats

作　　者：吕宾[1] 张璐[1] 范一宏[1] 徐毅[1] 

机构地区：[1]浙江中医药大学附属第一医院消化内科,杭州310006

出　　处：《中华医学杂志》2008年第4期220-224,共5页National Medical Journal of China

摘　　要：目的观察替普瑞酮对类固醇性溃疡大鼠胃黏膜热休克蛋白（HSP）70和c—fos表达的影响，探讨其保护作用和机制。方法50只雄性SD大鼠随机分为空白组、实验组、低剂量替普瑞酮组、中剂量替普瑞酮组和高剂量替普瑞酮组，每组10只。采用泼尼松龙皮下注射制备大鼠胃黏膜损伤模型，低、中、高剂量组替普瑞酮的剂量分别为50、100、200mg／kg，给药7d，每天1次。观察胃黏膜的病理变化，计算溃疡指数，免疫组化方法检测胃黏膜c—fos水平，RT—PCR方法检测大鼠胃黏膜HSP70mRNA的表达。结果类固醇激素能引起胃黏膜显著出血性损伤，实验组大鼠溃疡指数中位数为44．5，明显高于空白组（0，P〈0．01），实验组大鼠胃黏膜c—fos染色积分为42±8，高于空白组（22±3，P〈0．01），HSP70mRNA的相对表达量高于空白组（0．22±0．03VS0．04±0．02，P〈0．01）。低、中、高剂量替普瑞酮组的溃疡指数中位数分别为32．5，23．0，23．0，均明显低于实验组（均P〈0．01），大鼠胃黏膜c—fos染色积分分别为34±2，30±5，25±3，均明显低于实验组42±8（均P〈0．01）；HSP70mRNA的相对表达量分别为0．36±0．05，0．41±0．09，0．49±0．05，均明显高于实验组（0．22±0．03，均P〈0．01）。结论替普瑞酮对类固醇致胃黏膜损伤具有一定的保护作用，其机制可能与诱导HSP表达，抑制胃黏膜c—fos的表达有关，Objective To estimate the effect of teprenone on the expression of heat shock protein （ HSP）70 and c-fos in stomach following prednisolone ingestion. Methods Fifty male Sprague-Dawley rats were randomly into 5 equal groups： normal control group, undergoing gastric perfusion of normal saline （NS） for 7 days, and since the 4 th day undergoing fasting for 4 days; model control group, undergoing gastric perfusion of NS for 7 days, and since the 4 th day undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg for 4 days; and 3 model therapy groups, undergoing gastric perfusion with low, middle, and high dose of teprenone （50 mg/kg, 100 mg/kg, and 200 mg/kg respectively） for 7 days and undergoing fasting and subcutaneous injection of prednisolone 40 mg/kg since the 4 th day. Twenty-four hours after the last administration of drugs, the rats were killed with their stomachs taken ont. The gastric ulcer index （UI） was measured. HE staining was used to observe the injury index of the gastric mucosa. The mRNA expression of HSP70 in the gastric tissue was semi-quantitatively detected with reverse transcription-polymerase chain reaction. The protein expression of c-fos in the gastric tissue was detected with immunohistochemical staining. Results The injury index of the gastric mucosa of the model control group was 5.5, significantly higher than that of the normal control group （ 0, P = 0. 000 ） , and the injury indexes of the 3 teprenone groups were all significantly lower than that of the model control group dose- dependently （ all P 〈0.01 ）. The UI of the model control group was 44.5, significantly higher than that of the normal control group （0, P = 0. 000） , and the UI values of the 3 teprenone groups were 32.5,23.0, and 23.0 respectively, all significantly lower than that of the model control group dose-dependently （ all P 〈 0.01 ）. The expression value of c-fos of the model control group was 42± 8, significantly higher than that of the normal control group （ P 〈0

关 键 词：泼尼松龙 胃黏膜 热休克蛋白质类 

分 类 号：R686[医药卫生—骨科学]