Song Qing, Gao Hanjing, Wu Wen, Gao Yu, Yang Jihua, Jiao Ziyu, Luo Yukun
Department of Ultrasound, First Medical Center of General Hospital of Chinese PLA, Middle Street of 4th West Ring Road, Beijing, 100853, China.
Department of Ultrasound, General Hospital of Chinese PLA, Seventh medical center, Beijing, 100700, China.
Dig Dis Sci. 2023 Jan;68(1):138-146. doi: 10.1007/s10620-022-07497-6. Epub 2022 Apr 22.
We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model.
An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1 min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12 h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas.
SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1 h, 6 h, and 12 h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats.
Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.
我们之前已经表明甲磺酸加贝酯-泊洛沙姆407偶联物（GMTI）可减轻大鼠创伤性胰腺炎。在本研究中，我们在优化的大鼠模型中评估了GMTI对牛磺胆酸钠诱导的重症急性胰腺炎（SAP）的治疗效果。
通过微量注射3.5%牛磺胆酸钠并在胆管中保留1分钟建立SAP大鼠模型。对SAP大鼠通过尾静脉注射（i.v.）或尾静脉注射+腹腔注射（i.v.+i.p.）给予GMTI。所有大鼠在治疗后12小时处死。采用生化方法和酶联免疫吸附测定法测量血清淀粉酶（AMY）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。进行苏木精-伊红染色和TUNEL检测以检查大鼠胰腺的组织病理学和腺泡细胞凋亡情况。
所有模型大鼠均成功诱导出SAP，表现为SAP症状和体征逐渐加重、胰腺组织病理学异常以及血清TNF-α、IL-6和AMY水平升高。1小时、6小时和12小时的死亡率分别为0%、0%和25%。通过i.v.或i.v.+i.p.给予GMTI治疗可显著降低SAP大鼠的胰腺湿重、腹水量、病理评分以及TNF-α和IL-6的循环水平，同时促进腺泡细胞凋亡。在改善SAP大鼠胰腺组织学和降低TNF-α及IL-6血清水平方面，i.v.+i.p.给予GMTI治疗优于i.v.给予。
我们优化的SAP大鼠模型可靠且可重复。GMTI治疗是一种有前景的抗SAP方法。
