川芎嗪对慢性高氧肺损伤新生大鼠内源性一氧化氮合酶表达水平的影响

目的观察川芎嗪干预对新生大鼠高氧肺损伤的影响及可能作用机制。方法80只足月新生12h内的清洁级SD大鼠，随机分为空气组（A组）、空气＋川芎嗪组（B组）、高氧（60％）组（C组）、高氧＋川芎嗪组（D组）。B、D两组每日腹腔注射川芎嗪30mg／kg，一日一次，A、C两组每日腹腔注射等量生理盐水，实验第14天每组随机选取8只，测量体重后取肺组织，测量肺质量，HE染色观察肺组织病理改变并计算其放射状肺泡计数（RAC）、RT—PCR方法检测内皮型一氧化氮合酶（eNOS）mRNA表达水平；免疫组织化学染色法检测eNOS蛋白表达水平。结果C组显示明显的肺泡发育受阻，体重（g）、肺质量（g）、RAC值（个）较A、B组均明显减少体重：（17．4±3．2）比（29．5±1．7）、（29．3±1．6），肺质量：（0．26±0．04）比（0．41±0．03）、（0．40±0．03），RAC值：（4．8±0．7）比（9．0±0．8）、（8．8±0．9），P〈0．05]，D组病理改变减轻，体重、肺质量、RAC值高于C组（P〈0．05），与A组相近（P〉0．05）。与A组（3．54±0．37）相比，C组肺组织eNOS表达水平（2．76±0．23）明显降低，D组（3．80±0．36）表达较C组增加，差异有统计学意义（P〈0．05），与A组相近（P〉0．05）。结论高氧可导致新生大鼠出现肺损伤，病理改变类似于早产儿新型支气管肺发育不良，川芎嗪干预对其有一定保护作用，其机制可能与川芎嗪促进eNOS的表达并捅过内源性NO生成增多而降低肺微血管压力有美．

Protection effect of tetramethylpyrazine on hyperoxia induced lung injury in neonatal rats

Objective To investigate the effect of Tetramethylpyrazine on hyperoxia induced lung injury in neonatal rats. Methods Eighty Sprague-Dawley （SD） clean grade neonatal rats, all younger than 12 hours old, were randomly divided into 4 groups ： A ： room air control group ; B ： room air ＋ Tetramethylpyrazine treatment group ; C ： hyperoxia control group ; D ： hyperoxia ＋ Tetramethylpyrazine treatment group. Rats in the hyperoxia groups were continuously exposed to oxygen with FiO2 of 60%. Neonatal rats in groups B and D were injected with Tetramethylpyrazine 30 mg/（kg-d）] through intraperitoneal route; whereas, rats in groups A and C were injected with equal volume of normal saline （NS）. On the 14th day of experiment, eight rats from each group were randomly chosen and sacrificed. The weight of body and lung were measured. HE stain was used to observe pathological changes of lung tissue and radical alveolar count （RAC） under light microscope. Immunostaining and RT-PCR were used to detect the expression of eNOS changes. Results In comparison to rats in group A ＆ B, rats in group C that were exposed to hyperoxia environment have marked inhibition in lung development, with body weight, lung weight and RAC decreased dramatically. Treating hyperoxia-exposed rats with Tetramethylpyrazine not only significantly increased body and lung weights, but also the numbers of RAC （ P 〈 0.05 ） in these rats to the levels similar to the without hyperoxia damage （P 〈 0. 05 ）. Expression of eNOS was dramatically decreased in rats that were exposed to hyeroxia environment （ P 〈 0. 05 ）, but has demonstrated marked improvement after treatment with Tetramethylpyrazine close to the level of the control group （P 〈 0. 05 ）. Conclusions Hyperoxia exposure leads to lung injuries in neonatal rats with pathological changes similar to bronchopulmonary dysplasia. Tetramethylpyrazine partially prevents the development of BPD induced by hyperoxia probably by increasing the expression of eNOS.