胃黏膜巨噬细胞是否导致急性胰腺炎中的胃损伤？
Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?
作者信息
Dang Sheng-Chun, Wang Hao, Zhang Jian-Xin, Cui Lei, Jiang De-Li, Chen Rong-Fang, Qu Jian-Guo, Shen Xiang-Qian, Chen Min, Gu Min
机构信息
Sheng-Chun Dang, Hao Wang, Jian-Xin Zhang, Lei Cui, Rong-Fang Chen, Jian-Guo Qu, Department of General Surgery, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
出版信息
World J Gastroenterol. 2015 Mar 7;21(9):2651-7. doi: 10.3748/wjg.v21.i9.2651.
AIM
To investigate the protective effect of clodronate-containing liposomes against severe acute pancreatitis (SAP)-triggered acute gastric mucosal injury (AGMI) in rats.
METHODS
Clodronate- and phosphate-buffered saline (PBS)-containing liposomes were prepared by reverse-phase evaporation. The SAP rat model was established by injecting sodium taurocholate into the pancreatic subcapsular space. Sprague-Dawley rats were randomly divided into three groups: control (C), SAP plus PBS-containing liposome (P) and SAP plus clodronate-containing liposome (T). Serum tumor necrosis factor (TNF)-α levels were estimated by ELISA. Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin (HE) staining. Apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining.
RESULTS
The liposomes had a mean diameter of 150 ± 30 nm. The TNF-α levels were significantly higher in the P group than that in the C group (2 h, 145.13 ± 11.50 vs 23.2 ± 2.03; 6 h, 245.06 ± 12.11 vs 30.28 ± 6.07, P < 0.05), and they were significantly lower in the T group than that in the P group (2 h, 93.24 ± 23.11 vs 145.13 ± 11.50; 6 h, 135.18 ± 13.10 vs 245.06 ± 12.11, P < 0.05). The pathological scores of the pancreas were lower in the T group than in the P group (2 h, 1.88 ± 0.83 vs 4.13 ± 0.83; 6 h, 2.87 ± 0.64 vs 6.25 ± 0.88, P < 0.01). The pathological scores of the gastric mucosa were also lower in the T group than in the P group (2 h, 1.12 ± 0.64 vs 2 ± 0.75; 6 h, 1.58 ± 0.53 vs 3 ± 1.31, P < 0.05). In addition, increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group. Clodronate-containing liposomes decreased the CD68 levels in the mucosa of the T group. The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group (2 h, 15.7 ± 0.92 vs 11.5 ± 1.64; 6 h, 21.12 ± 1.06 vs 12.6 ± 2.44, P < 0.01).
CONCLUSION
Gastric macrophages contribute to the pathogenesis of gastric injury in SAP. Clodronate-containing liposomes have protective effects against AGMI in rats with SAP.
目的
探讨含氯膦酸盐脂质体对大鼠重症急性胰腺炎（SAP）引发的急性胃黏膜损伤（AGMI）的保护作用。
方法
采用逆相蒸发法制备含氯膦酸盐和磷酸盐缓冲盐水（PBS）的脂质体。通过向胰腺被膜下间隙注射牛磺胆酸钠建立SAP大鼠模型。将Sprague-Dawley大鼠随机分为三组：对照组（C）、SAP加含PBS脂质体组（P）和SAP加含氯膦酸盐脂质体组（T）。采用酶联免疫吸附测定（ELISA）法测定血清肿瘤坏死因子（TNF）-α水平。通过苏木精-伊红（HE）染色观察胃黏膜和胰腺的病理变化。采用末端脱氧核苷酸转移酶dUTP缺口末端标记染色检测凋亡细胞。通过CD68免疫组织化学染色分析胃黏膜中巨噬细胞的数量。
结果
脂质体的平均直径为150±30nm。P组的TNF-α水平显著高于C组（2小时，145.13±11.50对23.2±2.03；6小时，245.06±12.11对30.28±6.07，P<0.05），且T组的TNF-α水平显著低于P组（2小时，93.24±23.11对145.13±11.50；6小时，135.18±13.10对245.06±12.11，P<0.05）。T组胰腺的病理评分低于P组（2小时，1.88±0.83对4.13±0.83；6小时，2.87±0.64对6.25±0.88，P<0.01）。T组胃黏膜的病理评分也低于P组（2小时，1.12±0.64对2±0.75；6小时，1.58±0.53对3±1.31，P<0.05）。此外，与C组相比，P组胃黏膜中CD68水平升高。含氯膦酸盐脂质体降低了T组黏膜中的CD68水平。T组胃黏膜的凋亡指数高于P组（2小时，15.7±0.92对11.5±1.64；6小时，21.12±1.06对12.6±2.44，P<0.01）。
结论
胃巨噬细胞参与了SAP中胃损伤的发病机制。含氯膦酸盐脂质体对SAP大鼠的AGMI具有保护作用。
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