偏二甲肼的眼组织分布特征及刺激性实验研究

Experimental study on ocular tissue distribution characteristics and irritation of unsymmetrical dimethylhydrazine

  • 摘要:
    背景 偏二甲肼被广泛地用作战略导弹液体推进剂,眼睛作为人体暴露在外的器官,在作业过程中易受到偏二甲肼的侵害。
    目的 检测偏二甲肼在眼各组织和血液中的分布,观察偏二甲肼对眼刺激性反应表现,测量偏二甲肼染毒后兔眼结膜囊及房水pH值变化。
    方法 以推进剂级液态偏二甲肼建立兔眼染毒模型,分为正常对照组以及染毒后1 h、2 h、1 d、3 d、7 d组,采用气相色谱质谱法对眼各组织及血液中偏二甲肼含量进行检测,通过裂隙灯显微镜观察各组偏二甲肼眼刺激反应评分,使用光纤pH计测量偏二甲肼眼染毒后结膜囊及房水pH变化。
    结果 偏二甲肼在正常对照组眼各组织中均未检测到含量,染毒后1 h眼各组织中均检测到偏二甲肼,其中房水中偏二甲肼的含量最高达(716.23 ± 23.71) mg/kg;染毒后2 h,眼各组织中仍残留部分偏二甲肼,但较1 h时含量显著降低(P<0.001),而染毒后1 d、3 d、7 d眼各组织中均未检测出偏二甲肼含量,各组血液中均未检测到偏二甲肼。正常对照组兔眼刺激反应评分为0.00(IQR:0.00 ~ 0.00)分,偏二甲肼染毒1 h、2 h、1 d、3 d、7 d组中位评分分别为2.75(IQR:2.38 ~ 3.00)、5.00(IQR:4.63 ~ 5.25)、6.00(IQR:5.50 ~ 6.00)、4.00(IQR:4.00 ~ 5.50)、2.00(IQR:1.50 ~ 2.00)分,各组眼刺激反应评分差异有统计学意义(χ2=33.11,P<0.001)。pH测量结果:正常对照组,结膜囊8.34 ± 0.14,房水8.60 ± 0.26;偏二甲肼染毒1 h组,结膜囊8.53 ± 0.10,房水7.67 ± 0.16;偏二甲肼染毒2 h组,结膜囊8.50 ± 0.17,房水7.50 ± 0.09;偏二甲肼染毒1 d组,结膜囊7.91 ± 0.13,房水7.16 ± 0.12;偏二甲肼染毒3 d组,结膜囊7.87 ± 0.10,房水7.91 ± 0.17;偏二甲肼染毒7 d组,结膜囊7.54 ± 0.12,房水7.60 ± 0.20;各组兔眼结膜囊pH及房水pH差异有统计学意义(P<0.001)。
    结论 偏二甲肼推进剂在模拟实际作业环境下,可经眼前节角膜快速渗透至眼内各组织到达眼后节视网膜,房水中含量最高,偏二甲肼在眼内的代谢速度也很快。偏二甲肼对眼组织有轻度刺激性反应作用,仅限于眼角膜、结膜反应。推进剂级偏二甲肼原液呈弱碱性,眼染毒后结膜及房水pH变化短时间内与偏二甲肼渗透进入前房及眼前节组织损伤后炎症反应有关。

     

    Abstract:
    Background Dimethylhydrazine is widely used as a liquid propellant for strategic missiles, and the eyes, as the exposed organs of the human body, are susceptible to its damage during operation.
    Objective To detect the distribution of dimethylhydrazine in various tissues and blood of the eyes, observe the irritant response of dimethylhydrazine to the eyes, and measure the changes in pH values of the rabbit's conjunctival sac and aqueous humor after exposure to dimethylhydrazine.
    Methods The rabbit eye toxicity model was divided into normal control group and groups 1 h, 2 h, 1 d, 3 d, and 7 d after exposure to unsymmetrical dimethylhydrazine. Gas chromatography-mass spectrometry was used to detect the content of unsymmetrical dimethylhydrazine in the eye and the blood, the eye irritation response scores of each group were observed under a slit lamp microscope and a fiber optic pH meter was used to measure the pH changes in the conjunctival sac and aqueous humor.
    Results No levels of dimethylhydrazine were detected in the normal control group's ocular tissues. However, dimethylhydrazine was detected in all ocular tissues 1 hour after exposure, with the highest concentration in aqueous humor reaching (716.23 ± 23.71) mg/kg; After 2 hours some residual dimethylhydrazine was still present, but the content was significantly reduced compared to 1 hour (P<0.001). However, no dimethylhydrazine was detected in various tissues of the eyes at 1 d, 3 d, and 7 d after exposure, and no dimethylhydrazine was detected in the blood. The normal control group had a rabbit eye irritation response score of 0.00 (IQR: 0.00 - 0.00), while the groups exposed to dimethylhydrazine for 1 hour, 2 hours, 1 day, 3 days, and 7 days had scores of 2.75 (IQR: 2.38 - 3.00), 5.00 (IQR: 4.63 - 5.25), 6.00 (IQR: 5.50 - 6.00), 4.00 (IQR: 4.00 - 5.50), and 2.00 (IQR: 1.50 - 2.00), respectively. The difference in eye irritation response scores among different groups was statistically significant (χ2=33.11, P<0.001). The pH of the conjunctival sac and aqueous humor in the normal control group of rabbits was 8.34 ± 0.14 and 8.60 ± 0.26, and they were 8.53 ± 0.10 and 7.67 ± 0.16 in the 1 h group, 8.50 ± 0.17 and 7.50 ± 0.09 in the 2 h group, 7.91 ± 0.13 and 7.16 ± 0.12 in the 1 d group, 7.87 ± 0.10 and 7.91 ± 0.17 in the 3 d group , 7.54 ± 0.12 and 7.60 ± 0.20 in the 7 d group, with statistically significant differences (P<0.001).
    Conclusion Unsymmetric dimethylhydrazine can quickly penetrate into various tissues in the anterior segment of the cornea and reach the posterior segment of the retina, with the highest content in aqueous humor. However, the metabolism rate of unsymmetrical dimethylhydrazine is also very fast. Unsaturated dimethylhydrazine propellant has a mild irritating effect on eye tissue. The propellant grade solution exhibits weak alkalinity, and the pH changes in the conjunctiva and aqueous humor after eye infection are related to metabolic infiltration into the anterior chamber and an inflammatory response after tissue damage in the anterior segment of the eye.

     

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