胆囊收缩素在内毒素休克大鼠中的抗炎作用及其信号转导机制
Anti-inflammatory effect of cholecystokinin and its signal transduction mechanism in endotoxic shock rat.
作者信息
Meng Ai-Hong, Ling Yi-Ling, Zhang Xiao-Peng, Zhang Jun-Lan
机构信息
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China.
出版信息
World J Gastroenterol. 2002 Aug;8(4):712-7. doi: 10.3748/wjg.v8.i4.712.
AIM
To study the anti-inflammatory effects of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS)-induced endotoxic shock (ES) and further investigate its signal transduction pathways involving p38 mitogen-activated protein kinase (MAPK) and IkappaB-alpha.
METHODS
Eighty-four rats were divided randomly into four groups: LPS (8 mg.kg(-1), iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8 mg.kg(-1)); CCK-8 (40 microg.kg(-1), iv) or normal saline (control) groups. The inflammatory changes of lung and spleen, phagocytic function of alveolar macrophage, quantification of inflammatory cells in bronchoalveolar lavage (BAL) were investigated in rats by using hematoxylin and eosin (HE) staining, phagocytosis of Candida albicans and differential cell counting. Nitric oxide (NO) production in serum, lung and spleen was measured with the Griess reaction. The mechanism involving p38 MAPK and IkappaB-alpha signal pathways was investigated by Western blot.
RESULTS
Inflammatory changes of lung and spleen induced by LPS were alleviated by CCK-8, the increase of NO induced by LPS in serum, lung and spleen was significantly inhibited and the neutrophil infiltration in BAL was significantly reduced by CCK-8. The number of neutrophils was (52+/-10)X10(6) cells. (-1) in LPS group, while it decreased to (18+/-4)X10(6) cells. (-1) in CCK-8+LPS (P<0.01). The phagocytic rate of CCK-8 group increased to (62.49+/-9.49) %, compared with control group (48.16+/-14.20) %, P<0.05. The phagocytosis rate was (85.14+/-4.64) % in LPS group, which reduced to (59.33+/-3.14) % in CCK-8+LPS group (P<0.01). The results of phagocytosis indexes showed similar changes. CCK-8 may play an important role in increasing the expression of p38 MAPK and decreasing the degradation of IkappaB-alpha in lung and spleen of ES rats.
CONCLUSION
CCK-8 can result in anti-inflammatory effects, which may be related to activation of p38 MAPK and inhibition on the degradation of IkappaB-alpha.
目的
研究胆囊收缩素八肽（CCK-8）对脂多糖（LPS）诱导的内毒素休克（ES）的抗炎作用，并进一步探讨其涉及p38丝裂原活化蛋白激酶（MAPK）和IκB-α的信号转导途径。
方法
84只大鼠随机分为四组：LPS（8mg·kg⁻¹，静脉注射）诱导ES；CCK-8（40μg·kg⁻¹，静脉注射）在LPS（8mg·kg⁻¹）前10min预处理；CCK-8（40μg·kg⁻¹，静脉注射）组或生理盐水（对照组）。采用苏木精-伊红（HE）染色、白色念珠菌吞噬试验和细胞分类计数，观察大鼠肺和脾的炎症变化、肺泡巨噬细胞吞噬功能、支气管肺泡灌洗（BAL）中炎症细胞定量。用Griess反应测定血清、肺和脾中一氧化氮（NO）的产生。通过蛋白质印迹法研究涉及p38 MAPK和IκB-α信号通路的机制。
结果
CCK-8减轻了LPS诱导的肺和脾的炎症变化，显著抑制了LPS诱导的血清、肺和脾中NO的增加，CCK-8显著减少了BAL中的中性粒细胞浸润。中性粒细胞数量在LPS组为（52±10）×10⁶个细胞·⁻¹，而在CCK-8+LPS组降至（18±4）×10⁶个细胞·⁻¹（P<0.01）。CCK-8组吞噬率升至（62.49±9.49）%，与对照组（48.16±14.20）%相比，P<0.05。LPS组吞噬率为（85.14±4.64）%，在CCK-8+LPS组降至（59.33±3.14）%（P<0.01）。吞噬指数结果显示类似变化。CCK-8可能在增加ES大鼠肺和脾中p38 MAPK表达及减少IκB-α降解中起重要作用。
结论
CCK-8可产生抗炎作用，这可能与激活p38 MAPK和抑制IκB-α降解有关。
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