摘要目的 观察山楂承气汤对高脂血症性急性坏死性胰腺炎(HANP)大鼠肠道毛细血管内皮屏障功能障碍的治疗效果,探讨其可能的机制.方法 雄性Sprague-Dawley大鼠120只,按数字表法随机分为高脂血症组(HL)、HANP组、辛伐他汀组和山楂承气汤组.采用高脂饲料喂养4周加静脉注入Triton WR1339的方法制备高胆固醇、高三酰甘油血症模型,后3组再采用腹腔内注射雨蛙素和脂多糖的方法制备急性坏死性胰腺炎(ANP)形成HANP模型.辛伐他汀组于HANP制模前2h及制模后2、4、12h分别用辛伐他汀药液灌胃1次,每次2.6 mg/kg体质量.山楂承气汤组同时间点灌胃1次,每次2 ml汤剂.制模后6、12、24 h分别处死大鼠,处死前1h经阴茎静脉注入2％伊文思蓝染料.检测各组大鼠血清淀粉酶、三酰甘油(TG)、游离脂肪酸(FFA)、连接黏附分子C(JAM-C)含量;观察肠壁组织形态学及超微结构改变;检测肠壁组织毛细血管通透性及JAM-C mRNA表达量.结果 与HL组比较,HANP组大鼠血清JAM-C、TG、FFA含量差异无统计学意义,但血清淀粉酶活性显著升高[(4963±531)U/L比(885±28) U/L,P＜0.01],肠壁的病理组织学及超微结构损伤显著加重,肠壁组织毛细血管通透性及JAN-C mRNA表达量(4.46±0.16比2.08±0.35)均显著升高,差异均有统计学意义(P＜0.01).与HANP组比较,山楂承气汤组淀粉酶活性[(991±61) U/L比(4963±531) U/L]、TG含量[(20.68±2.68) mmol/L比(95.73±2.19) mmol/L]、FFA含量[(1238±37) μmol/L比(3879 ±64) μmol/L]、JAM-C含量[(166.44±10.26) ng/L比(396.99±12.15) ng/L]均显著下降(P值均＜0.01),肠壁的病理组织学及超微结构损伤显著减轻,肠壁组织毛细血管通透性及JAM-C mRNA表达量(1.38± 0.10比4.46±0.16)均显著下降,差异均有统计学意义(P值均＜0.01).辛伐他汀组各指标的下降程度均低于山楂承气汤组.结论 山楂承气汤可以改善HANP大鼠的病情,减轻肠壁组织毛细血管渗漏,其机制可能与下调肠壁组织JAM-C的表达有关.

abstractsObjective To investigate the therapeutic efficacy of Shanzhadachengqi Decoction on the capillary endothelial cell barrier dysfunction of the intestinal tract in hyperlipidemic acute necrotizing pancreatitis (HANP) rats,and to explore the possible molecular mechanism.Methods Male Sprague-Dawley rats (n =120) were randomly divided into hyperlipidemic (HL) group,HANP group,simvastatin group and Shanzhadachengqi Decoction(SD) group.The hyperlipidemic model was established by 4 weeks fat-rich food and Triton WR1339 intravenous injection.The rats in the latter 3 groups underwent intraperitoneal injection of cerulein and lipopolysaccharid to induce the acute necrotizing pancreatitis (ANP) (HANP model).The rats in simvastatin group received simvastatin gastric lavage (2.6 mg/kg) 2 h before HANP model induction,2,4,12 h after HANP model induction,while the rats in SD group received Shanzhadachengqi Decoction gastric lavage (2 ml) at the same time points,then the rats were sacrificed at 6,12,and 24 h after model induction.One hour before the rats were sacrificed,they were injected with 2％ Evens Blue.Levels of serum amylases,triacylglycerol (TG),free fatty acid (FFA) and junctional adhesion molecule C (JAM-C) were examined; the pathological changes and ultramicrostructure in intestine tissues were observed; expression of JAM-C mRNA and capillary permeability in intestine tissues were determined.Results The serum levels of JAM-C,TG,FFA in HANP group was not significantly different from those in the HL group,but the serum level of amylase was significantly increased [(4 963 ± 531) vs (885 ± 28) U/L,P =0.003].The pathology change and the ultramicrostructure showed histopathological changes in intestine tissues in HANP group were more severe,and the intestine tissular capillary permeability [(201.83 ± 8.50) vs (54.23 ± 5.79) μg/ml,P =0.000],the expression of JAM-C mRNA [(4.46 ±0.16) vs (2.08 ±0.35),P=0.002)] was significantly higher than those in the HL group,and the difference between the two groups was statistically significant (P ＜ 0.05).Compared with HANP group,the serum level of amylases [(991 ±61) vs (4 963 ±531)U/L,P=0.003],TG [(20.68 ± 2.68) vs (95.73 ± 2.190 mmol/L,P =0.000],FFA [(1 238 ± 37) vs (3 879 ± 64) μmol/ L,P=0.000],JAM-C [(166.44± 10.26) vs (396.99± 12.15) ng/L,P=0.000] in SD group were significantly decreased.Pathology change and the ultramicrostructure showed histopathological changes in intestine tissues were attenuated.The intestine tissular capillary permeability [(39.90 ± 3.62) vs (201.83 ± 8.50) μg/ml,P =0.000],the expression of JAM-C mRNA [(1.38 ± 0.10) vs (4.46 ± 0.16),P =0.003] were significantly decreased,and the difference between the two groups was statistically significant (P ＜ 0.05).The decreased degree of corresponding values in simvastatin group wsa lower than those in SD group.Conclusions Shanzhadachengqi Decoction can improve the course of HANP rat; and relieve the intestine tissuior capillary leakage,which may be related with the down-regulation of JAM-C expression in intestine tissues.