Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.
Mol Biol Rep. 2012 Apr;39(4):3557-63. doi: 10.1007/s11033-011-1129-z. Epub 2011 Jul 3.
To explore the influence of vasoactive intestinal peptide (VIP) on the gut barrier function in severe acute pancreatitis (SAP). Fifty four SD rats were randomly divided into three groups: sham operated (SO) group, SAP group and VIP intervention group. Each group was further divided into three time points: 1, 6 and 12 h after operation with 6 rats for each treatment point. SAP models were induced by retrograde injection of 4% sodium taurocholate into the bili-pancreatic duct. VIP intervention group was made by 5 nmol VIP intraperitoneal injection within 5 min after SAP model successfully obtained. The VIP in plasma and intestinal homogenate were detected with ELISA. The endotoxin in plasma of all groups was also tested. The expression levels of TLR4, TNF-α, IL-6, and IL-10 in gut mucosa were measured by RT-PCR. Meanwhile intestinal samples were harvested for pathological examination. Compared to SO group, the VIP in plasma and intestinal homogenate of SAP group were significantly decreased at 1 h after induction, and then gradually increased to beyond the level of SO group at 12 h. The endotoxin of SAP group was continually increased. The mRNA levels of TLR4, TNF-α, IL-6, and IL-10 were also increased with obvious pathological injuries in the intestine. In the VIP group, endotoxin in plasma was obviously decreased compared to SAP group. The expressions of TNF-α, IL-6 mRNA were suppressed while IL-10mRNA was increased. The intestinal pathological injuries were also markedly alleviated. These results suggested that VIP had protective effects on SAP gut barrier function through inhibiting intestinal mucosal inflammatory responses.
探讨血管活性肠肽(VIP)对重症急性胰腺炎(SAP)肠屏障功能的影响。
将 54 只 SD 大鼠随机分为三组:假手术(SO)组、SAP 组和 VIP 干预组。每组再分为 3 个时间点:术后 1、6 和 12 h,每个时间点 6 只大鼠。通过逆行胰胆管注射 4%牛磺胆酸钠制备 SAP 模型。SAP 模型成功建立后 5 min 内,VIP 干预组通过腹腔注射 5 nmol VIP。采用 ELISA 法检测各组大鼠血浆和肠组织匀浆 VIP 含量,检测各组大鼠血浆内毒素含量。采用 RT-PCR 法检测各组大鼠肠黏膜 TLR4、TNF-α、IL-6 和 IL-10 表达水平。同时采集肠组织标本进行病理学检查。
与 SO 组相比,SAP 组大鼠诱导后 1 h 血浆和肠组织匀浆 VIP 明显下降,12 h 时逐渐升高至超过 SO 组水平。SAP 组内毒素持续升高。TLR4、TNF-α、IL-6 和 IL-10 的 mRNA 水平也随之升高,肠道出现明显的病理损伤。VIP 组大鼠血浆内毒素明显低于 SAP 组,TNF-α、IL-6mRNA 表达受到抑制,IL-10mRNA 表达增加,肠道病理损伤明显减轻。
VIP 对 SAP 肠屏障功能具有保护作用,其机制可能与抑制肠道黏膜炎症反应有关。