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还原型辅酶Ⅱ氧化酶抑制剂夹竹桃麻素对重症急性胰腺炎大鼠肠道损伤的保护作用 被引量:5

The protective effect of apocynin, nicotinamide adenine dinucleotide phosphate oxidase inhibitor, on intestinal mucosal barrier injury in severe acute pancreatitis in rats
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摘要 目的探讨还原型辅酶Ⅱ(NADPH)氧化酶抑制剂夹竹桃麻素(Apocynin)对大鼠重症急性胰腺炎(SAP)大鼠肠道损伤的的保护作用及其机制。方法雄性Wistar大鼠48只,随机分为假手术组(SO组,n=8)、重症急性胰腺炎组[SAP组,按时间分3、12、24h亚组(n=8)]、Apocynin预处理组(APO组,n=8)、Apocynin药物对照组(APO-CON组,n=8)。SAP大鼠胆胰管逆行注射5%牛磺胆酸钠制备SAP模型。APO组造模同SAP组,在造模前30rnin股静脉注射Apocynin(50mg/kg),SO组仅翻动胰腺后关腹,APO-CON组仅行股静脉注射Apocynin(50mg/kg),余同S0组。全自动生化仪检测各组大鼠血清淀粉酶(AMY)及脂肪酶(HP)水平。苏木素一伊红(HE)染色观察各组胰腺组织及回肠组织病理改变。采用免疫组织化学法检测p38丝裂原活化蛋白激酶(p38MAPK)、磷酸化p38丝裂原活化蛋白激酶(p—p38MAPK)及核转录因子-κB(NF—κB)回肠组织的表达。透射电镜下观察回肠黏膜上皮细胞超微结构改变。结果与SO组AMY、LIP胰腺病理评分及回肠病理评分(1236.00±155.72、90.50±9.60、0.24±0.07、0.34±0.18)比较,SAP组大鼠血清AMY、HP、胰腺和回肠病理评分升高明显(4918.20±389.63、1712.90±103.80、12.45±1.01、3.50±0.31,P〈0.05)。APO组上述指标明显下降(3698.00±386.93、659.40±92.40、8.76±1.34、2.20±0.36)。APO—CON组上述指标与SO组比较差异无统计学意义(P〉0.05)。SAP组肠组织光镜下可见损伤严重,APO组光镜下回肠组织病理损伤较SAP组减轻。免疫组织化学检查显示SAP组大鼠回肠组织p38、P-p38及NF—κB表达较SO组与APO—CON组升高明显(P〈0.05),APO组上述指标均明显下降(P〈0.05)。电镜下可见APO组大鼠回肠黏膜上皮细胞超微结构改变较SAP组减轻。光镜下及电镜下,SO组及APO—CON组均无明显� Objective To investigate the protective effect of apocynin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, on Intestinal injury associate with severe acute pancreatitis in rats. Methods Fourty - eight male Wistar rats were randomly divided into four groups : Sham operation group ( SO group, n = 8 ) , Severe acute pancreatitis model group ( SAP group, n = 24 ) , apocynin treatment group ( APO group, n = 8 ) , apocynin drug control group ( APO - CON, n = 8 ). SAP group was divided into three time points of 3, 12 and 24 h ( n = 8 at each time point). SAP model was prepared by retrograde infusing 5% sodium taurocholate ( 1 ml/kg) into bilio - pancreatic duct of the rats. In APO group, apocynin (50 mg/kg)was administrated via femoral vein 30 min prior to the operation, other procedures were identical to the SAP group. In SO group, pancreas flipped several times only. In drug control group, apocynin (50 mg/kg)was administrated via femoral vein 30 min prior to the operation, other procedures were identical to the SO group. The levels of serum amylase, lipase were measured. Take fresh pancreas and ileum tissues make pathological slides and observe histopathological changes under a light microscope. The expression of p38 Mitogen - activated protein kinase ( p38MAPK), phosphorylated p38 Mitogen - activated protein kinases ( p - p38MAPK) and nuclear factor kappa B ( NF - KB) were measured by using immunohistochemistry assay. The ultra - struetue of mucosal epithelial cell of intestine was observed by electron microscope. Results Serum amylase, seruin lipase, pancreatic and ileus pathological scores were significantly higher in SAP group (4 918. 20 ±389. 63, 1 712. 90 ± 103.80, 12. 45 ± 1.01,3.50 ±0. 31 ) compared with SO group ( 1 236.00 ± 155.72, 90. 50 ± 9. 60, 0. 24 ± 0. 07, 0. 34 ± 0. 18, P 〈 0. 05 ). And they were significantly lower in APO group compared with SAP group (P 〈 0. 05 ). Expression of p38MAPK, P - p38MAPK and
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2016年第1期19-25,共7页 Chinese Journal of Experimental Surgery
基金 国家自然科学基金(81360081/H0320) 湖北省自然科学基金(2013CFB458) 武汉大学自主科研项目(2042015KF0090)
关键词 重症急性胰腺炎 肠黏膜损伤 还原型辅酶Ⅱ氧化酶 Severe acute pancreatitis Intestinal injury Nicotinamide adenine dinucleotide phosphate oxidase
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