番茄红素对急性肺损伤大鼠免疫细胞和炎性细胞因子的影响

目的:研究番茄红素对急性肺损伤(acute lung injury,ALI)大鼠T淋巴细胞亚群及肺泡巨噬细胞(pulmonary alveolar macrophages,PAM)功能的影响,探讨番茄红素对ALI的可能作用及其机制.方法:不同剂量番茄红素给大鼠连续灌胃35 d后,腹腔注射脂多糖(lipopolysaccharide,LPS)6.0 mg/kg建立ALI模型(对照用生理盐水),分别在注射后1 h,4 h和6 h收集腹主动脉血并进行左侧支气管肺泡原位灌洗以收集灌洗液;测定血中淋巴细胞亚群、PAM吞噬功能及肿瘤坏死因子α(tumor necrosis factor,TNF-α)和白细胞介素8(interleukin-8,IL-8)浓度.结果:(1) CD3+,CD4+,CD8+T细胞百分比在1 h各组间差异无统计学意义.4 h时,CD3+T细胞百分比高剂量组[(28.8±9.9)%]显著低于正常对照组[(39.5±4.5)%];CD8+T细胞百分比在ALI模型对照组,番茄红素低、中、高剂量组分别是(10.2±3.9)%,(10.3±2.8)%,(9.8±2.8)%,(10.1±3.5)%,均显著低于正常大鼠[(15.1±2.5)%].6 h时,番茄红素低、中剂量组与对照组相比CD3+T和CD8+T细胞百分比显著降低.ALI大鼠CD4+/CD8+值在4 h时升高,且番茄红素低、中剂量组与正常对照组比较差异有统计学意义.(2)1 h时,正常对照组,ALI模型对照组,番茄红素低、中、高剂量组PAM在540 nm下光密度分别为0.136±0.025,0.215±0.095,0.239±0.052,0.275±0.068和0.297±0.049,可见ALI大鼠PAM吞噬功能较正常大鼠显著增强;4 h和6 h时情况与1 h相似.(3)正常对照组,ALI模型对照组,番茄红素低、中、高剂量组支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中TNF-α浓度分别为1.50±0.30,1.87±0.30,1.76±0.40,1.74±0.38,1.62±0.35 μg/L;IL-8浓度分别为0.82±0.08,0.99±0.14,0.82±0.16,0.84±0.16,0.83±0.11 μg/L,ALI模型对照组均显著高于正常对照组.结论:番茄红素能增强ALI大鼠PAM吞噬功能并抑制炎性因子TNF-α、IL-8的产生,可能起到减轻ALI大鼠肺损伤程度和改善预后的作用.

Effect of lycopene on immunity in rats with acute lung injury

OBJECTIVE: To investigate the effects of lycopene on T lymphocyte subpopulations and pulmonary alveolar macrophagic (PAM) functions in rats with acute lung injury (ALI). METHODS: Rats were randomly divided into the following groups. (1) Control group, (2) ALI model group, (3) Low dose group,(4) Mid dose group and (5) High dose group. Control group and ALI model group were treated with solvent of lycopene, and the other groups were gastrically incubated with lycopene. Thirty-five days later, control group were given physiological saline, ALI model group and lycopene administrated groups were injected with lipopolysaccharide (LPS) (6.0 mg/kg) to induce ALI. One hour, four hours or six hours after LPS or physiological saline challenged, abdominal aorta blood for measuring lymphocyte subpopulations and bronchoalveolar lavage fluid for measuring function of PAM were gathered respectively. RESULTS: (1) At h 1, the percentages of CD3(+), CD4(+) and CD8(+) of lycopene administrated groups compared with control group were not significantly different. At h 4, the percentage of CD4(+) was similar to that at h 1. As for the percentages of CD3(+), except high dose group [(28.8+/-9.9)%] was significantly lower, low dose, mid dose and ALI model group showed no significant difference compared with control group[(39.5+/- 4.5)%]. The percentages of CD8(+) of ALI model and lycopene administrated rats, separately (10.2+/-3.9)%, (10.3+/-2.8)%, (9.8+/-2.8)%, (10.1+/-3.5)% , had been significantly reduced compared with control group[(15.1+/-2.5)%]; between ALI model and lycopene administrated groups there was no significant difference. The instance at h 6 was the same as that at h 4. The percentage ratios of CD4(+) T-lymphocyte to CD8(+) T-lymphocyte of ALI model rats were not significantly different compared with control group or lycopene administrated groups at h 1 and h 6. At h 4, the ratio of the CD4(+) and CD8(+) in Low dose and Mid dose groups had significant difference and ALI model, high dose hadn't when they were compared with control group. (2) Lycopene increased the phagocytic function of PAMs significantly at h 1(P<0.01), the optical density of PAM of control group, ALI model group, low dose group, mid dose group, high dose group was 0.136+/-0.025, 0.215+/-0.095, 0.239+/-0.052, 0.275+/-0.068 and 0.297+/-0.049; what happened at h 4 was similar to that at h 1; Phagocytic function of PAM of lycopene administrated groups was increased compared with control group. (3) The concentrations of tumor necrosis factor-alpha (TNF-alpha) in control group, ALI model group, low dose group, mid dose group, high dose groups were 1.50+/-0.30, 1.87+/-0.30, 1.76+/-0.40, 1.74+/- 0.38,1.62+/-0.35 microg/L;and those of IL-8 were 0.82+/-0.08, 0.99+/-0.14, 0.82+/-0.16, 0.84+/-0.16, 0.83+/-0.11 microg/L. The concentrations of TNF-alpha and interleukin-8 (IL-8) in BALF were decreased by lycopene, especially the levels of IL-8 were reduced significantly. CONCLUSION: Lycopene might attenuate lipopolysaccharide-induced impairment of lungs and improve ALI prognosis by increasing the phagocytic function of PAMs significantly and restraining the secretion of TNF-alpha and IL-8.