丙泊酚对大鼠脑创伤继发肺损伤的影响

Effects of propofol on lung injury secondary to traumatic brain injury in rats

目的探讨丙泊酚（PPF）对创伤性脑损伤（TBI）大鼠肺损伤和应激的影响。方法36只SD雄性大鼠按随机数字表法分为假手术（sham）组、脂肪乳组、TBI组、PPF1h组、PPF2h组和PPF6h组，每组6只。液压冲击制作TBI模型，腹腔注射给药，脂肪乳组在假手术后给予脂肪乳，PPF组在伤后1，2，6h注射丙泊酚100mg／kg。评价神经运动功能；测定血清促肾上腺皮质激素（ACTH）、皮质醇（COR）和去甲肾上腺素（NE）浓度；伤后72h处死PPF2h组大鼠，取肺行光镜和电镜检查。单因素方差分析和t检验进行统计学处理。结果与sham组和脂肪乳组比较，TBI组出现神经功能障碍，ACTH、COR和NE浓度显著升高（P均〈0．01）。丙泊酚各组神经功能障碍明显减轻，ACTH、COR和NE浓度显著低于TBI组（P均〈0．01），PPF1h组和PPF2h组间差异无统计学意义（t=-0．816，t=-0．208，t=0．582，P均〉0．05），PPF2h组COR和NE浓度分别为（250．60±34．10）μg/L、（2646．08±263．61）pg／mL，显著低于PPF6h组[（314．73±39．33）μg／L＆（3364．87±402．14）]（t=3．018，P=0．013；t=3．662，P=0．004）。光镜下，TBI组肺间质增宽，肺泡内纤维素样渗出物和炎性细胞浸润。电镜下，TBI组肺Ⅱ型上皮细胞肿胀变性，胞质见嗜锇板层小体排空，微绒毛样突起减少。PPF2h组渗出物和炎性细胞减少，细胞肿胀减轻。结论丙泊酚可能通过控制创伤应激对TB｜大鼠肺损伤起保护作用，且使用越早效果越好。

Objective To evaluate the effect of propofol （PPF） on stress response and lung injury in rats with traumatic brain injury （TBI）. Methods A total of 36 SD rats were randomly （random number） divided into sham group, intralipid group, TBI group, PPF1 h group, PPF 2 h group, PPF 6 h group （ n = 6 in each group）. Fluid percussion brain injury models were used. By intraperitoneal injection, intralipid was administered in intralipid group after sham operations, while propofol 100 mg~ kg- t was given to rats in PPF1 h group, PPF 2 h group and PPF 6 h group 1, 2, 6 hours following injury, respectively. Nerve motor function were scored at different intervals, serum concentrations of adrenocorticotropic hormone （ACTH）, cortisol （COR） and norepinephrine （NE） were measured 12 h after injury. Seventy-two hours later, all rats were sacrificed and brains were harvested for TFC staining, and lungs taken were stained with HE staining for observation under light microscope and electron microscopy. Results Compared with sham and intralipid group, nerve motor function scores were significantly decreased, and serum concentrations of ACTH, COR and NE were increased significantly in rats after injury. Compared with TBI group, the above biomarkers were improved significantly after propofol injection. There were no significant differences in above biomarkers between PPF 1 h and PPF 2 h group （t = -0. 816, t = -0.208, t =0. 582, P 〉0.05） . The differences in COR and NE concentrations between PPF 2 h and PPF 6 h group were statistically significant （ t = 3. 018, P = 0. 013 ; t = 3. 662, P = 0. 004 ）. Light microscopy demonstrated abundant inflammatory cell infiltration and massive thickening of the alveolar walls, Electron microscopy showed Type Ⅱ lung epithelial cell swelling, vacuolar degeneration, osmiophilic lamellar corpuscle emptying in cytoplasm, mierovilli protrusions decreases in some cytoplasm in TBI group, and pathological damage was improved significantly in PPF 2 h group. Conclusions Propofol may inhibit stress and protect the lung tissue from damage in TBI rats.