论文部分内容阅读
目的探讨栗精胺(CS)对重症急性胰腺炎(SAP)大鼠肾损伤的保护作用及其可能的分子机理。方法将24只SPF级成年雄性SD大鼠随机分为假手术组(SO组)、SAP组和CS组,每组8只大鼠。采用逆行胰胆管注射5%牛磺胆酸钠溶液(1 mL/kg)的方法建立大鼠SAP肾损伤模型。CS组大鼠在SAP建模后立即经腹腔注射CS生理盐水溶液(200 mg/kg)。SO组大鼠开腹后仅翻动十二指肠及胰腺后关腹。建模后12 h处死大鼠,采集3组大鼠的血清、胰腺及肾脏组织标本。采用全自动多功能生化分析仪检测大鼠血清中的尿素氮(BUN)水平、肌酐(Cr)水平及淀粉酶(AMY)活性;采用HE染色并在光镜下观察大鼠胰腺及肾脏组织的病理学改变;采用免疫组织化学染色法检测3组大鼠肾脏组织中核因子-κB(NF-κB)、肿瘤坏死因子-α(TNF-α)、细胞间黏附分子-1(ICAM-1)及含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)蛋白的表达。结果 (1)在胰腺及肾脏病理损伤程度方面,SAP组大鼠较SO组严重,但CS组大鼠却较SAP组有所减轻。(2)与SO组比较,SAP组大鼠的血清Cr水平、BUN水平及AMY活性均较高(P<0.05);与SAP组比较,CS组大鼠的血清Cr水平、BUN水平及AMY活性均较低(P<0.05)。(3)与SO组比较,SAP组大鼠肾脏组织中NF-κB、TNF-α、ICAM-1及Caspase-3蛋白的积分光密度值(IOD值)均较高(P<0.05);与SAP组比较,CS组大鼠肾脏组织中NF-κB、TNF-α、ICAM-1及Caspase-3蛋白的IOD值均较低(P<0.05)。结论 CS可减轻SAP大鼠的急性肾损伤,其机制可能是通过抑制NF-κB的活化,下调下游炎性介质如TNF-α和ICAM-1蛋白的表达,以及抑制凋亡蛋白Caspase-3的表达来发挥保护作用的。
Objective To investigate the protective effect of castrate (CS) on renal injury in rats with severe acute pancreatitis (SAP) and its possible molecular mechanism. Methods Twenty-four SPF adult male Sprague-Dawley rats were randomly divided into sham operation group (SO group), SAP group and CS group, with 8 rats in each group. The rat model of SAP renal injury was established by injecting 5% sodium taurocholate solution (1 mL / kg) into the pancreatic duct through retrograde cholangiopancreatography. CS rats were injected intraperitoneally with CS saline solution (200 mg / kg) immediately after SAP modeling. In the SO group, only open the duodenum and the pancreas and open the abdomen. Rats were sacrificed at 12 h after modeling, and serum, pancreatic and renal tissues of 3 groups of rats were collected. The levels of serum urea nitrogen (BUN), creatinine (Cr) and amylase (AMY) in serum of rats were detected by automatic multi-functional biochemical analyzer. HE staining and optical microscope were used to observe the changes of pancreatic and renal tissues The pathological changes were observed by immunohistochemistry. The expressions of nuclear factor-κB, tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) Expression of caspase-3 containing cysteine. Results (1) In the pathological damage of pancreas and kidney, the SAP group was more serious than the SO group, but the CS group rats were relieved compared with the SAP group. (2) Compared with SO group, serum Cr level, BUN level and AMY activity in SAP group were higher (P <0.05). Compared with SAP group, serum Cr level, BUN level and AMY activity Lower (P <0.05). (3) Compared with SO group, the integral optical density (IOD) values of NF-κB, TNF-α, ICAM-1 and Caspase-3 protein in SAP group were higher than those in SO group Compared with SAP group, the IOD values of NF-κB, TNF-α, ICAM-1 and Caspase-3 in kidney of CS group were lower (P <0.05). Conclusion CS can relieve acute renal injury in SAP rats by down-regulating the expression of TNF-α and ICAM-1, and inhibiting the expression of Caspase-3, an inhibitor of NF-κB To play a protective role.