低分子肝素对急性坏死性胰腺炎并肝损伤P-选择素和E-选择素表达的影响

目的研究低分子肝素(LWMH)对大鼠急性坏死性胰腺炎(ANP)并肝损伤中P-选择素和E-选择素表达的影响及其对急性坏死性胰腺炎的保护作用。方法将96只雄性SD大鼠随机分为三个组:对照组(C组,n=32)、急性坏死性胰腺炎组(A组,n=32)、低分子肝素干预组(G组,n=32)。A组以1.5%脱氧胆酸钠溶液逆行注入胰胆管建立急性坏死性胰腺炎模型(1 ml/kg),G组于造模后给予皮下注射低分子肝素(10 U/100 g),C组仅翻动胰腺后关腹。各组分别于造模后6、12、24、48 h四个时点分批处死大鼠,测定血清淀粉酶水平;E LISA检测血清TNF-α、IL-6水平,取胰腺及肝脏组织光镜下进行病理学评分;RT-PCR检测肝脏P-选择素和E-选择素mRNA表达。结果三组间和不同时点之间各项观察指标比较均有统计学意义(P0.01),A组6、12、24、48 h各时点胰腺及肝脏病理评分、血清淀粉酶及TNF-oα、IL-6水平,P-选择素和E-选择素mRNA表达均较C组相应时点显著升高(P0.05);G组各时点胰腺及肝脏病理评分、血清淀粉酶及TNF-oα、IL-6水平,P-选择素和E-选择素mRNA表达均较A组对应时点显著降低(P0.05)。结论 P-选择素和E-选择素在急性坏死性胰腺炎并肝损伤时的表达可能与病变严重程度有关;LWMH可能是通过下调P-选择素和E-选择素表达减轻急性坏死性胰腺炎的胰腺和肝脏病变。

Effects of low molecular weight heparin on the expression of P-selectin and E-selectin in necrotizing acute pancreatitis associated with liver injury

Objective To investigate the expression of P-selectin and E-selectin in acute necrotizing pancreatitis (ANP)associated with liver injury in rats,and evaluate the effect of low molecular weight heparin(LMWH). Methods Ninety-six Sprague-Dawley rats were-randomly and equally divided into control group(group C,n=32), ANP group(group A,n=32)and LMWH intervention group(group G,n=32).In group A,the rats was induced retrograde injection of 1.5%sodium deoxycholate into the biliary-pancreatic duct to induce ANP(1 ml/kg).In group G, after modeling,subcutaneous low molecular weight heparin calcium(10 U/100 g).In group C.the abdomen was closed only after turning the pancreas.The rats were killed at 6 hours,12 hours,24 hours and 48 hours.The level of serum amylase was detected.The level of serum TNF-a and IL-6 was determined by ELISA.The pathologic changes of pancreas and liver were observed and graded under the microscope.The expression of P-selectin mRNA and E-selectin mRNA in liver were evaluated by RT-PCR.Results The comparison of each observation index of the three groups and different time points reached statistical significance(P<0.01),At each time point,the pathologic scores of the pancreas and liver,the level of serum-amylase and TNF-α、IL-6 in serum,the expression of P-selectin mRNA and Eselectin mRNA in liver of group A were significantly higher than group C(P<0.05),while the pathologic scores of the pancreas and liver,the level of serum-amylase and TNF-α、IL-6 in serum,the expression of P-selectin mRNA and E-selectin mRNA in group G were significantly lower than group A(P<0.05).Conclusion The expression of P-selectin and E-selectin may concerned with the level of liver injury in acute necrotizing pancreatitis.LMWH may alleviate liver injury by its inhibition of the expression of P-selectin and E-selectin in acute necrotizing pancreatitis.