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目的探讨4-苯基丁酸(4-phenylbutyric acid,PBA)对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠肝损伤的影响及可能的分子机制。方法采用逆行胰胆管注射5%牛磺胆酸钠溶液(1 mL/kg)建立大鼠SAP肝损伤模型,将24只成年雄性SPF级SD大鼠随机分为假手术组(SO组)、SAP组和PBA组,每组8只。PBA组在SAP造模前3 d经腹腔注射PBA生理盐水溶液(50 mg/kg),SAP组及SO组则经腹腔注射等体积的生理盐水。造模后12 h处死大鼠,采集各组大鼠的血液、胰腺及肝组织,采用全自动多功能生化分析仪检测大鼠血清淀粉酶(amylase,AMY)、谷丙转氨酶(alanine aminotransferase,ALT)及谷草转氨酶(aspartate transaminase,AST)的含量变化;苏木精-伊红(HE)染色光镜下观察大鼠胰腺及肝脏的形态学变化;免疫组织化学法检测各组大鼠肝脏葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)、CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer binding protein homologous protein,CHOP)及Caspase-3的表达。结果 SAP组血AMY、ALT和AST水平,胰腺病理学评分,肝脏病理学评级以及肝脏GRP78、CHOP和Caspase-3蛋白的表达均高于SO组(P<0.05),除AMY水平外(P>0.05),PBA组上述各项指标与SAP组相比均降低(P<0.05)。结论 PBA有减轻SAP肝损伤的作用,其机制可能与抑制内质网应激(ERS)并减少细胞凋亡有关。
Objective To investigate the effect and possible molecular mechanism of 4-phenylbutyric acid (PBA) on liver injury in rats with severe acute pancreatitis (SAP). Methods The rat model of hepatic injury induced by SAP was established by injecting 5% sodium taurocholate solution (1 mL / kg) into the pancreaticobiliary duct. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham operation group Group and PBA group, 8 rats in each group. The rats in PBA group were injected intraperitoneally with PBA saline solution (50 mg / kg) 3 days before SAP model injection. The rats in SAP group and SO group were injected intraperitoneally with equal volume of normal saline. Rats were sacrificed at 12 h after model establishment. Blood, pancreas and liver tissues were collected from all the rats. Serum amylase (AMY) and alanine aminotransferase (ALT) were detected by automatic multifunctional biochemical analyzer. ) And aspartate transaminase (AST). The morphological changes of the pancreas and liver were observed under hematoxylin-eosin (HE) staining. The hepatic glucose regulation was detected by immunohistochemistry Glucose-regulated protein 78 (GRP78), CCAAT / enhancer binding protein homologous protein (CHOP) and Caspase-3. Results The serum levels of AMY, ALT and AST, the scores of pancreatic pathology, liver pathology and the expressions of GRP78, CHOP and Caspase-3 in SAP group were significantly higher than those in SO group (P < 0.05). The above indexes in PBA group were lower than those in SAP group (P <0.05). Conclusion PBA can reduce the hepatic injury induced by SAP. Its mechanism may be related to the inhibition of endoplasmic reticulum stress (ERS) and the decrease of apoptosis.