首页> 中文期刊> 《安徽医科大学学报》 >乌司他丁对爆炸致家兔急性肺损伤的作用及机制

乌司他丁对爆炸致家兔急性肺损伤的作用及机制

         

摘要

Objective To research the effect and mechanism of Ulinastatin ( UTI) on acute lung injury in rabbits induced by blast .Methods The model of acute lung injury in rabbits was induced by blast .According to the ran-domized table, all the rabbits were randomly divided into 5 groups, normal group, ALI group, low-dose UTI group, medial-dose UTI group and high-dose UTI group.When the models of acute lung injury were finished , the rabbits in UTI groups were intravenously injected with different doses of UTI (2.5 ×104,5 ×104,10 ×104 U/kg), while the rabbits in normal group and ALI group were injected with normal saline of same doses .The blood was collected after 4 hours and the bronchial alveolar lavage fluid ( BALF ) , blood and some lung tissues were saved after 24 hours.TNF-α, IL-6, IL-10 were determined by ELISA method .NF-κB was evaluated by Western blot and the re-verse transcription polymerase chain reaction .The wet to dry weight ratios ( W/D) were determined .The patholog-ical changes of lung tissues were observed under the microscope .Results The levels of W/D, TNF-α, IL-6 , NF-κB in ALI group were significantly higher than those in normal group ( P<0.05) .With the treatment of UTI , the values of W/D, TNF-αand IL-6 in UTI groups of different doses were lower than their measures in ALI group .On the contrary , the IL-10 in ALI group was lower than that in other groups ( P<0.05 ) .Between these comparisons , high-dose UTI group was the most significant group ( P<0.05 ) .Histopathology of lung tissue showed that pulmo-nary edema and inflammatory in medial-dose and high-dose UTI group were better than those in ALI group .Con-clusion UTI could relive inflammation in the lungs of rabbits with ALI induced by blast through balancing excess release of cytokines and inflammatory mediators , UTI could be a potential drug of ALI .%目的:探讨乌司他丁( UTI )对爆炸致家兔急性肺损伤( ALI)的作用及其机制。方法选择家兔40只,随机分为5组:正常组、ALI组和UTI低剂量组、UTI中剂量组、UTI高剂量组,每组8只,建立家兔ALI动物模型后,UTI低、中、高剂量组分别注射2.5×104、5×104、10×104 U/kg UTI溶液,正常组、ALI组注射等量生理盐水。4 h采集血液,24 h采集支气管肺泡灌洗液( BALF)、血液及肺组织标本,并测定肺湿干重比( W/D),ELISA法测定BALF及血清中肿瘤坏死因子-α( TNF-α)、白介素-6( IL-6)、白介素-10( IL-10)的含量,Western blot法和反转录PCR法测定肺组织核转录因子-κB( NF-κB)蛋白和mRNA的表达水平,光镜下观察肺HE切片病理学变化。结果 ALI组W/D、TNF-α、IL-6以及NF-κB表达量均较正常组升高( P<0.05), UTI低、中、高剂量组的W/D、TNF-α、IL-6表达量均较ALI组降低( P<0.05), UTI低、中、高剂量组 IL-10表达量较 ALI 组明显提高( P <0.05),且三次比较中,均以UTI高剂量组作用最显著(P<0.05);肺病理切片显示UTI中、高剂量组肺水肿、炎症反应等较ALI组减轻。结论 UTI可通过调控炎症反应时细胞因子的产生和释放,减轻爆炸致家兔ALI的肺部损伤程度,以高剂量作用最明显,UTI可能成为一个潜在的治疗ALI的药物。

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