Zhang Xiao-Hua, Zhu Ren-Min, Xu Wen-An, Wan Hai-Jun, Lu Heng
Department of Gastroenterology, Jinling Hospital, Nanjing 210002, Jiangsu Province, China.
World J Gastroenterol. 2007 Jan 28;13(4):623-7. doi: 10.3748/wjg.v13.i4.623.
To assess the therapeutic effect of Caspase-1 inhibitors (ICE-I) on acute lung injury (ALI) in experimental severe acute pancreatitis (SAP).
Forty-two SD rats were randomly divided into 3 groups: healthy controls (HC, n = 6); SAP-S group (n = 18); SAP-ICE-I group (n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum IL-1beta was measured by ELISA. Intrapulmonary expression of Caspase-1, IL-1beta and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated.
Serum IL-1beta levels in SAP-S group were 276.77 +/- 44.92 pg/mL at 6 h, 308.99 +/- 34.95 pg/mL at 12 h, and 311.60 +/- 46.51 pg/mL at 18 h, which were increased significantly (P < 0.01, vs HC). In SAP-ICE-I group, those values were decreased significantly (P < 0.01, vs SAP-S). Intrapulmonary expression of Caspase-1, IL-1beta and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group (P < 0.01, vs HC). The expression of IL-1beta and IL-18 mRNA were decreased significantly in the SAP-ICE-I group (P < 0.01, vs SAP-S), whereas Caspase-1 mRNA expression had no significant difference (P > 0.05). The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly (P < 0.05 at 6 h, P < 0.01 at 12 h and 18 h, vs HC) and they were decreased significantly in the SAP-ICE-I group (P < 0.05, vs SAP-S). Caspase-1 inhibitors ameliorated the severity of ALI in SAP.
Caspase-1 activation, and overproduction of IL-1beta and IL-18 play an important role in the course of ALI, and Caspase-1 inhibition is effective for the treatment of ALI in experimental SAP.
评估半胱天冬酶-1抑制剂（ICE-I）对实验性重症急性胰腺炎（SAP）所致急性肺损伤（ALI）的治疗效果。
42只SD大鼠随机分为3组：健康对照组（HC，n = 6）；SAP-S组（n = 18）；SAP-ICE-I组（n = 18）。通过向胆胰管逆行输注5%牛磺胆酸钠诱导SAP。HC组大鼠接受相同手术操作及胆管插管，但不输注牛磺胆酸钠。在SAP-S组，大鼠在急性胰腺炎诱导后2小时首次腹腔注射等渗盐水，并在12小时后重复注射。在SAP-ICE-I组，大鼠在胰腺炎诱导后2小时首先腹腔注射ICE抑制剂。与SAP-S组一样，在12小时重复注射。采用ELISA法检测血清白细胞介素-1β（IL-1β）。通过半定量逆转录-聚合酶链反应（RT-PCR）检测肺组织中半胱天冬酶-1、IL-1β和IL-18 mRNA的表达。同时评估肺组织的湿/干重比及组织病理学变化。
SAP-S组血清IL-1β水平在6小时为276.77±44.92 pg/mL，12小时为308.99±34.95 pg/mL，18小时为311.60±46.51 pg/mL，均显著升高（与HC组相比，P < 0.01）。在SAP-ICE-I组，这些值显著降低（与SAP-S组相比，P < 0.01）。HC组肺组织中可观察到半胱天冬酶-1、IL-1β和IL-18 mRNA的表达，而在SAP-S组中显著增加（与HC组相比，P < 0.01）。在SAP-ICE-I组中，IL-1β和IL-18 mRNA的表达显著降低（与SAP-S组相比，P < 0.01），而半胱天冬酶-1 mRNA表达无显著差异（P > 0.05）。SAP-S组肺组织的湿/干重比显著增加（与HC组相比，6小时P < 0.05，12小时和18小时P < 0.01），而在SAP-ICE-I组中显著降低（与SAP-S组相比，P < 0.05）。半胱天冬酶-1抑制剂可改善SAP中ALI的严重程度。
半胱天冬酶-1的激活以及IL-1β和IL-18的过度产生在ALI病程中起重要作用，抑制半胱天冬酶-1对实验性SAP中的ALI治疗有效。
