热休克蛋白70减轻大鼠急性坏死性胰腺炎机制的实验研究  

Experimental study on the mechanism of the HSP70 in reducing acute necrotizing pancreatitis of rats

作　　者：程书榜[1] 李林林[1] 朱量[1] 秦颖[1] 

机构地区：[1]深圳市第二人民医院胃肠外科,深圳518035

出　　处：《中国医师杂志》2014年第1期17-20,共4页Journal of Chinese Physician

基　　金：广东省科技局资助项目（20118031800355）

摘　　要：目的 探讨热休克蛋白70减轻大鼠急性坏死性胰腺炎的机制.方法 80只SD大鼠随机分为4组,急性坏死性胰腺炎模型组（A）、假手术组（B）、温生理盐水腹腔灌洗预处理后急性坏死性胰腺炎（ANP）组（C）和温生理盐水腹腔灌洗和丝裂原活化蛋白激酶p38（p38MAPK）抑制剂（SB202190）预处理后ANP组（D）,ANP模型由5%牛黄胆酸钠大鼠胰胆管逆行注射诱发而成.C组使用温生理盐水持续腹腔灌洗30 min,10 h后造ANP模型;D组在使用温生理盐水腹腔冲洗后,立刻行SB202190（10 mg/kg）腹腔注射,10 h后制造ANP模型.ANP术后6 h处死大鼠,检查各组大鼠血清细胞因子IL-6、TNF-α和IL-8;血清淀粉酶;取胰腺组织行病理检查,并使用PCR方法检测胰腺中热休克蛋白70（HSP70）/p38-MAPK的表达.结果 SB202190预处理组大鼠血清淀粉酶[（1779.77±84.90）U/L]和温生理盐水腹腔灌洗预处理组[（2845.70＆#177;204.78）U/L]明显低于ANP组[（4064.93±188.97）U/L,P＜0.05],但高于假手术组[（1221.47±54.58）U/L,P＜0.05];SB202190预处理组低于温生理盐水腹腔灌洗预处理组（t＝3.329,P＜0.05）.SB202190预处理组和温生理盐水腹腔灌洗预处理组大鼠血清TNF-α、IL-6、IL-8明显低于ANP组（P＜0.05）,但高于假手术组（P＜0.05）;SB202190预处理组低于温生理盐水腹腔灌洗预处理组（P＜0.05）.SB202190预处理组和温生理盐水腹腔灌洗预处理组胰腺组织p38MAPK mRNA含量明显低于ANP组（P＜0.05）,温生理盐水腹腔灌洗预处理组高于假手术组（P＜0.05）;SB202190预处理组低于温生理盐水腹腔灌洗预处理组（P＜0.05）.结论 HSP70可以通过调控p38MAPK从而下调细胞因子的表达,进而改善大鼠ANP病理生理.Objective To explore the mechanism of heat shock protein 70 （HSP70） in reducing acute necrotizing pancreatitis （ANP）. Methods A total of 80 Sprague-Dawley （SD） rats was randomly divided into group A （ acute necrotizing pancreatitis）, group B （sham-operated）, group C （warm saline pretreatment ANP）, and group D [ warm saline and mitogen-activated protein kinase （p38MAPK） inhibitor（SB202190） pretreatment ANP], with 20 rats in each group. ANP model was induced by retrograde injection of 5% sodium tauroeholate to rat pancreatic duct. Group C using physiological saline celiac lavage for 30 minutes, ANP model was made after 10 hours. In group D, after physiological saline celiac lavage, SB202190 （10 mg/kg） was given by intraperitoneal injection, and made ANP after 10 hours. The rats were sacrificed at the 6th hours after ANP operation. Serum levels of tumor necrosis factor-~, Inter- leukin-6 （IL-6）, IL-8, and amylase were measured by enzyme-linked immunosorbent assay （ELISA）. The pancreas tissues were ob- tained to examine the change with microscope, the expressions of HSP70 and p38MAPK were examined by polymerase chain reaction （PCR） method. Results The level of serum amylase in group C[ （2845.70 ±204. 78）U/L]was significantly lower than in group A, but higher than that in group B[ （ 1221.47 ±54. 58）U/L] and group D [ （1779. 77 ±84. 90）U/L] （ P 〈 0. 05 ）. The level of serum TNF-α, IL-6 and IL-8 in the peritoneal lavage group were lower than the ANP group but were higher than the sham-operated group and the SB202190 pre-management group （ P 〈0. 05）. In group C, the level of p38MAPK lower than that in ANP group （ P 〈0.05）. The level of p38MAPK mRNA in peritoneal lavage pretreated group was significantly lower than the ANP group , but higher than the sham group and SB202190 pretreatment group （ P 〈 0. 05 ）. Pancreatic pathological damages were much milder in groups D and C than those in group A under microscope. Conclusions Through dow

关 键 词：HSP70热休克蛋白质类 胰腺炎 急性坏死性 动物实验 

分 类 号：R576[医药卫生—消化系统]