八肽胆囊收缩素对大肠杆菌致急性肺损伤大鼠的抗炎作用

Inflammation inhibitive effect of CCK-8 on acute lung injury rats induced by Escherichia coli

目的探讨八肽胆囊收缩素（CCK-8）对大肠杆菌致急性肺损伤（ALI）大鼠肺水肿及炎症反应的抑制作用。方法将45只雄性SD大鼠按随机数字表法分为3组，ALI／急性呼吸窘迫综合征（ARDS）组、ALI／ARDs＋CCK8组和对照组。ALI／ARDS组气管注射大肠杆菌制作ALI／ARDs模型；ALI／ARDS＋CCK8组于注射大肠杆菌后8h制成ALI／ARDS模型，再静脉注射CCK8（60ug／kg）。分别于12h、24h后检测动脉血气判定氧合指数；24h后处死大鼠取肺脏，测量肺脏湿／干重比；流式细胞术检测肺组织细胞凋亡率；荧光免疫法检测肺血内皮素1。结果ALI／ARDs＋CCK-8组与ALI／ARDS组比较，氧合指数明显增高（12h：312±25VS249±37，P〈0．01；24h：297±39VS168±44，P〈0．001），肺脏湿／干重比下降（4．28±0．23VS4．87±0．29，P〈O．05），肺泡腔及间质水肿和炎细胞浸润较轻，肺脏细胞凋亡率明显减低，内皮素1的水平降低（P〈0．05）。结论外源性CCK8能明显抑制ALI／ARDS大鼠肺脏炎症反应，减少肺水肿程度，保护肺血管，提高氧合指数，减轻了ALI／ARDs症状。

Objective To explore the inhibitive effects and potential mechanisms of CCK-8 on ALI/ ARDS of infected rats induced by E. eoli injection. Methods Forty-five SD male rats were randomly divided into control group, ALI/ARDS group, and ALI/ARDS＋CCK 8 group. ALI/ARDS model was induced in rats by 0.9% normal saline E. eoli injection. The rats of ALI/ARDS±CCK-8 group was injected by CCK-8 （60 ug . kg-1 ） 8 h after E. eoli injection, and the control group rats were injected by 0.9% normal saline in trachea. 12 h and 24 h after E. eoli or 0.9% normal saline intratracheal injection, PaO2/FiO2 was recorded, and at 24 h after injetion lung wet/dry ratio, microscopic examination and apoptosis of lung tissue were examined, and endothelin 1 （ET-1） was detected by radioimmunoassay. Results Compared with those of ALI/ARDS group, the PaO2/FiO2 was significantly higher （12 h.. 312±25 vs 249±37, P 〈0.01;24 h：297±39 vs 168±44, P 〈0.001）, the lung wet/dry ratio was decreased （4.28 ± 0.23 vs 4.87±0.29, P 〈 0.05）, and alveolar edema and interstitial edema and infiltration of inflammatory cells were unconspicuous under microscope. The apoptosis index of lung tissue and were significantly lower compared with ALI/ARDS group （ P 〈 0.05）. The ET 1 was significantly decreased in ALI/ARDS ＋ CCK-8 group （ P 〈 0.05）. Conclusions Taken together the findings indicate that CCK-8 can inhibit the inflammatroy reaction of ALI/ARDS in rats pneumonia, relieve lung edema, protect the lung cells, downregulat the ET-1 and reduce the vascular leakage function, and increase PaO2/FiO2. The CCK 8 can better the ALI/ARDS clinical symptom significantly.