[^(18)F]FDG microPET在评价二次打击所致大鼠急性肺损伤中的应用

Evaluation of the inflammatory response in two-hit acute lung injury model of rats using [^(18)F] FDG microPET

目的:对一次打击和二次打击进行深入的对比研究,应用[18F]-氟脱氧葡萄糖(FDG)小动物正电子断层扫描仪(microPET)对肺内的炎症反应进行评价。方法:将33只SD雄性大鼠随机分为4组,分别为生理盐水(NS)组(n=3):生理盐水1mL/kg腹腔注射(ip)及16h后生理盐水0.5mL/kg气道内滴入(it);脂多糖(LPS)组(n=10):LPS5mg/kgip及16h后生理盐水0.5mL/kgit;HCl组(n=10):生理盐水1mL/kgip及16h后HCl(pH=1.2,0.5mL/kg,it);二次打击LPS-HCl组(n=10):LPS5mg/kgip及16h后HCl(pH=1.2,0.5mL/kg,it)。在盐酸或生理盐水气道滴入前,所有大鼠戊巴比妥钠腹腔注射麻醉,行股动脉插管,连续监测平均动脉压(MAP),并于it后0.5h、1.5h及4h后抽血,查动脉血气分析,it后4h行[18F]FDG micro PET胸部扫描,然后处死动物,取肺组织进行组织病理学观察。结果:血气分析显示LPS-HCl大鼠低氧血症和二氧化碳潴留显著;MAP在气道内滴入盐酸或生理盐水前无差异,但在滴入后,LPS-HCl组中MAP较其它3组显著降低;micro PET示感兴趣区(ROI)在右肺与右上肢肌肉之间的比值进行比较,LPS-HCl组中此比值为9.00±1.41,显著高于LPS组4.01±0.60(P<0.01)和HCl组3.33±0.55(P<0.01);肺损伤病理评分在LPS-HCl组中为12.70±0.95,显著高于HCl组8.40±1.26(P<0.01)和LPS组7.00±0.82(P<0.01)。结论:二次打击可使机体肺内产生剧烈而且持久的炎症反应,比一次打击更容易诱发急性肺损伤;microPET作为一种无创的检测手段,能很好地评价急性肺损伤时肺内的炎症反应。

AIM ： To investigate whether two - hit acute lung injury （ALI） model is better than one - hit, and to evaluate the inflammatory response in the lungs during these models by using [^18F] FDG microPET. METHODS： Thirty three, adult, male Sprague - Dawley rats weighing 180 - 210 g were used and divided into 4 groups. Rats in LPS group （n = 10） and LPS- HCl group （n = 10） were challenged with intraperitoneal administration of LPS at the dose of 5 mg/kg, while rats in NS group （n = 3 ） and HCl group （n = 10） received normal saline solution intraperitoneally at the dose of 1 mL/kg, after 16 h, all animals were anesthetized with an intraperitoneal injection of sodium pentobarbital （40 mg/kg） and placed in a 60°inclined position, the femoral artery was cannulated and connected to a pressure transducer to record the arterial pressure on a polygraph recorder, the trachea was surgically exposed. Rats in HCl group and LPS - HCl group received direct intratracheal injection of HCI （ pH = 1.2） at the dose of 0. 5 mL/kg while rats in NS group and LPS group received the same volume of normal saline solution. Blood gas samples （ each 0.3 mL） were obtained at 30, 90 and 240 min after the instillation and replaced by the same volume of saline solution, the samples were analyzed using a blood gas analyzer. 240 min after HCI or NS administration, the rats underwent a microPET scanning, then, all the rats were sacrificed and the lungs were obtained for histological analysis. RESULTS ： Blood gas analysis showed that rats in LPS - HCl group had higher PaO2 and lower PaCO2 than the other groups. MAP decreased markedly in LPS - HCl group, while MAP in oth-er groups remained stable. The results of microPET showed that the ratio of ROI between the right lung and the muscle tissue of the right arm in LPS - HCl group was 9. 00 ± 1.41, and was significantly higher than that in LPS group （4. 01 ± 0. 60 ） and HCl group （3.33 ± 0. 55 ）. Histological examination showed that the mean lung injury score in LPS - HCl group was 12. 70±0. 95, while that was 8.40 ±1.26 in HCl group and 7.00 ± 0.82 in LPS group, and there were significant differences （ both P 〈 0. 01 ）. CONCLUSION ： LPS pretreatment significantly magnifies and prolongs the inflammatory re- sponse to the subsequent acid instillation in both lungs. When compared with ＂one - hit＂, ＂two - hit＂ is easier to induce the ALI, and [^18F] FDG microPET is a useful tool to evaluate the inflammatory reaction during ALI.