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氮硝基左旋精氨酸对烟雾吸入性损伤大鼠肺保护作用的研究

发布时间:2018-08-26 17:09
【摘要】:目的:把烟雾吸入性损伤大鼠做为本次试验的研究对象,对其腹腔注射氮硝基左旋精氨酸(Nω-Nitro-L-Arginine, L-NNA),观察不同剂量、不同作用时长L-NNA的治疗效果,明确并评价L-NNA对烟雾吸入性损伤大鼠的肺保护作用。方法:将60只大鼠随机分为4组,分别为空白组、致伤组、低剂量组和高剂量组,其中空白组6只大鼠不致伤,其余3组分为6h、24h、48h三个时相点,各组各时相点6只大鼠,在特制装置中用烟雾致伤。空白组不予任何处理,致伤组、低剂量及高剂量组于伤后立即各自腹腔注射等容量的生理盐水、浓度分别为1Omg/kg的L-NNA和20mg/kg的L-NNA。每只大鼠股动脉取血5ml,离心后检测血清白细胞介素-6(Interleukin-6, IL-6)、白细胞介素-10(Interleukin-10, IL-10)、肿瘤坏死因子-α(Tumomecrosis factor-α, TNF-α)含量,活杀后取部分左侧肺组织匀浆后检测丙二醛(Malondialdehyde, MDA)、髓过氧化物酶(Myeloperoxidase, MPO)及超氧化物歧化酶(Superoxide dismutase, SOD)含量,取部分右肺经4%甲醛溶液固定后做病理HE染色切片光镜观察。 结果:低剂量组24h、48h和高剂量组6h、24h、48h的TNF-α、IL-6含量与同时相点致伤组相比明显下降(P0.01),低剂量组6h和高剂量组6h、24h、48h的MDA、MPO含量与同时相点致伤组相比明显降低(P0.01),高剂量组6h、24h、48h的IL-10、SOD含量与同时相点致伤组相比明显升高(P0.01),高剂量组6h、24h、48h的IL-6、TNF-α、MDA、MPO含量比同时相点低剂量组明显降低(P0.01), IL-10、SOD含量相比同时相点低剂量组明显升高(P0.01)。低剂量组大鼠6h、24h、48h和高剂量组大鼠6h、24h、48h肺系数与同时相点致伤组大鼠相比有显著降低(P0.01),与低剂量组同时相点大鼠相比,高剂量组大鼠肺系数均有明显降低(P0.01),病理切片显示低剂量组6h和高剂量组6h大鼠相较致伤组6h肺组织肺水肿减轻,中性粒细胞、淋巴细胞等炎细胞的浸润减少,肺泡萎陷程度降低,其中高剂量组比低剂量组肺间质和肺泡内渗出减少。 结论:氮硝基左旋精氨酸可减轻大鼠吸入性损伤后肺组织中炎症反应及过氧化反应,从而减轻肺损伤的程度,而高剂量组比低剂量组的肺保护作用更好。
[Abstract]:Objective: to observe the therapeutic effect of long L-NNA in rats with smoke inhalation injury by intraperitoneal injection of N 蠅 -Nitro-L-Arginine (L-NNA). To determine and evaluate the protective effect of L-NNA on lung injury induced by smoke inhalation in rats. Methods: sixty rats were randomly divided into 4 groups: blank group, injury group, low dose group and high dose group. Among them, 6 rats in blank group were not injured, and the other three groups were divided into 3 groups: 6 rats in each group, and 6 rats in each group. To cause injuries with smoke in a special device. No treatment was given in the blank group. The injured group, the low dose group and the high dose group were intraperitoneally injected with normal saline of equal volume immediately after injury. The concentrations of L-NNA of 1Omg/kg and L-NNA of 20mg/kg were respectively. Serum interleukin-6 (Interleukin-6, IL-6), interleukin-10 (Interleukin-10, IL-10) and tumor necrosis factor- 伪 (TNF- 伪) were measured after centrifugation. The contents of malondialdehyde (Malondialdehyde, MDA),) myeloperoxidase (Myeloperoxidase, MPO) and superoxide dismutase (Superoxide dismutase, SOD) were detected in the homogenate of some left lung tissues. The pathological sections of the right lung were fixed with 4% formaldehyde solution and observed under light microscope. Results: the content of TNF- 伪 IL-6 in low dose group (24 h) and high dose group (6 h / 24 h) was significantly lower than that in simultaneous point group (P0.01). The content of MDA,MPO in low dose group (6 h) and high dose group (6 h) was significantly lower than that in simultaneous phase group (P 0.01). The IL-10,SOD in high dose group was significantly lower than that in high dose group (6 h, 24 h and 48 h). The content of IL-6,TNF- 伪 -MDA-MPO in the high dose group was significantly lower than that in the low dose group (P0.01), and the content of IL-10,SOD in the high dose group was significantly higher than that in the low-dose group at the same phase point (P0.01). The content of MDA-MPO in the high-dose group was significantly higher than that in the low-dose group at the same time (P0.01). The lung coefficients of the rats in the low dose group and the high dose group were significantly lower than those in the simultaneous phase point group (P0.01), and compared with those in the low dose group (P0.01). The lung coefficients of the rats in the high dose group were significantly decreased (P0.01). Pathological sections showed that lung edema, infiltration of neutrophils, lymphocytes and other inflammatory cells in the lung tissue of the rats in the low dose group at 6 h and in the high dose group at 6 h were less than those in the injured group at 6 h after injury (P0.01), and the infiltration of inflammatory cells such as neutrophils and lymphocytes decreased. The degree of alveolar collapse was decreased, and the interstitial and alveolar effusion in high dose group was lower than that in low dose group. Conclusion: nitro-L-arginine can reduce the inflammatory reaction and peroxidation in lung tissue after inhalation injury in rats, thus reducing the severity of lung injury. The protective effect of high dose group is better than that of low dose group.
【学位授予单位】:天津医科大学
【学位级别】:硕士
【学位授予年份】:2013
【分类号】:R644

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