鼠吸入全氟异丁烯急性肺损伤红花苷干预研究

Carthamin ameliorate acute lung injury in rats after perfluoroisobutylene exposing

目的探讨鼠吸入全氟异丁烯(PFIB)致急性肺损伤(ALI)模型应用红花苷干预的意义。方法 Wistar雄性大鼠130只随机分成实验组(30只,包括3个亚组)、染毒组(30只)和正常组(10只),分为24 h、72 h、7 d三个时间观察点,每个时间点各10只。正常组不染毒、不干预处理;而染毒组仅染毒,无药物干预;3个实验组均在染毒后1 h腹腔给药干预,实验组1单纯给红花,实验组2给红花联合地塞米松;实验组3给红花联合乌斯他丁;染毒组腹腔注射盐水;分别在不同时间点放血处死。观察肺含水量、支气管肺泡灌洗液(BALF)蛋白含量、血清和肺组织中的肿瘤坏死因子-α(TNF-α),用ELISA法测定白介素-1(IL-1),IL-8,IL-18,IL-10和P-选择素(P-s)。结果肺含水量以24 h最高;染毒组[(81.95±2.05)%]、实验组(3组)[(81.57±2.31)%、(83.57±3.35)%、(80.41±1.51)%]与正常组[(78.18±1.34)%]比较差异有高度统计学意义(P<0.01);3个实验组中以实验组组3最低,与实验组2和染毒组比较差异有统计学意义(P<0.05)。BALF蛋白含量,正常组[(0.32±0.25)g/L]与染毒组[(6.16±2.14)g/L]和实验组(3组)[(5.64±1.97)、(6.01±3.55)、(5.23±2.79)g/L]比较,差异均有高度统计学意义(P<0.01);实验组3与染毒组、实验组1、2比较,差异无统计学意义(P>0.05),但以实验组3最低。24 h实验组各组血清细胞因子TNF-α、IL-1、IL-8、IL-18低于染毒组,其中实验组1、实验组2 TNF-α[(14.06±6.08)、(6.92±14.10)μg/L]和IL-18[(64.94±11.84)、(66.93±11.69)μg/L]与染毒组TNF-α[(20.20±4.70)μg/L],IL-18[(87.34±20.98)μg/L]比较,差异均有统计学意义(P<0.05)。肺组织中相同细胞因子明显高于血清,在时间点的变化趋势与血清基本一致。结论红花苷可以降低PFIB吸入性ALI炎性细胞因子水平,联合乌斯他丁能更有效减轻肺水肿。

Objective To study carthamin treating effect for acute lung injury （ALI） in mice after exposing periluo roisobutylene （PFIB）. Methods 130 Wistar male rats were randomly divided into experiment groups （30 rats, including 3 subgroup）, contamination group （30 rats） and normal group （10 rats）, at 24 h, 72 h, 7 d and 3 different observing time points, 10 rats were researched in every time point. No poison and drug were given in normal group. The drugs were in jected into peritoneal cavity, carthamin only injected in experiment group 1; carthamin and dexamethasone in experi ment group 2, carthamin and urinastain injected in experiment group 3. The saline was injected into peritoneal cavity in the contamination group at 1 h after PFIB exposed. The rats in 3 experiment groups and contamination group were died by bloodletting. The water content of the lung, the protein level of the bronchoalveolar lavage （BALF） were evalu ated, and TNFo, IL1, IL8, IL18, IL10 and Pselectin of serum and pulmonary tissue were measured with ELISA. Results At time point of 24 h, the lung water content in each group was the highest; the lung water content in contami nation group [（81.95±2.05） %] and experimental groups [（81.57±2.31） %, （83.57±3.35） %, （80.41±1.51） %] were com pared with that in normal group [（78.18±1.34） %], the differences were statistically significant （P 〈 0.01）; in the 3 ex periment groups, the lung water content in experiment group 3 was the lowest, compared with those in experiment group 1 and experiment group 2, the differences were statistically significant （P 〈 0.05）. The protein content of BALF in nor mal group [（0.32＋0.25） %] was compared with those in contamination group [（6.16±2.14） g/L] and 3 experiment groups[（5.64±1.97）, （6.01±3.55）, （5.23±2.79） g/L], the differ ences were statistically significant （P 〈 0.01）; the protein content in experiment group 3 was compared with those in contamination group, experiment group ! and experiment group 2, the differece was not statistically significant （P 〉 0.05）, but that in experiment group 3 was the lowest. The serum cytokine TNFct, IL1, IL8, IL18 at time point of 24 h, these in experimental groups were lower than control group, TNFct in experiment group 1 and experiment group 2 [（14.06±6.08）, （6.92±14.10） μg/L] and IL18 in experiment group 1 and experiment group 2 [（64.94±11.84）, （66.93±11.69） μg/L] were compared with those in contami nation group [TNFa （20.20±4.70） μg/L, IL18 （87.34±20.98） μg/L], the differences were statistically significant （P 〈 0.05）. The above cytokine in pulmonary tissue was obviously higher than serum, the variation trend at each time point were the same in serum. Conclusion Carthamin may decrease inflammatory cytokine level of ALI after PFIB exposed, the usage of carthamin combined urinastain can further alleviate the pneumonedema.