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目的观察瘦素(LP)在矽肺模型大鼠肺组织的表达和对肺组织纤维化的影响以及与低氧诱导因子1α(HIF-1α)的相关性。方法 120只SD大鼠随机分为正常对照组、矽肺模型组、LP干预组(根据LP浓度分为LP5干预组、LP10干预组、LP20干预组)。对照组大鼠气管内灌注1 mL生理盐水,其余各组大鼠气管内灌注1 mL SiO2混悬液(40 mg/mL),从造模后1 d开始,LP5、LP10及LP20干预组分别给予5 ng/kg·d、10 ng/kg·d、20 ng/kg·d LP腹腔注射,第7天、14天、21天、28天各组分别处死6只大鼠。采用ELISA检测4个时间点各组大鼠肺组织LP的表达以及第28天羟脯氨酸含量。应用Western blot法测定矽肺模型组大鼠肺组织LP及HIF-1α蛋白表达。结果相同时期各组肺组织LP表达差异均有统计学意义(P<0.05),矽肺模型组显著高于正常对照组,3个不同浓度LP干预组均高于矽肺模型组(P<0.05)。第28天羟脯氨酸含量在正常对照组、矽肺模型组、LP5干预组、LP10干预组、LP20干预组分别为(0.89±0.16)mg/g、(3.14±0.40)mg/g、(3.78±0.27)mg/g、(4.35±0.13)mg/g、(4.87±0.16)mg/g,矽肺模型组LP表达较正常对照组明显增加(P<0.05),LP干预组LP表达均显著高于矽肺模型组(P<0.05)。各时间点模型组HIF-1α与LP的表达均呈正相关(r=0.88,0.79,0.86,0.85,P<0.05)。结论 LP在矽肺模型大鼠肺组织表达增加,增加外源性LP,能增加矽肺大鼠肺组织胶原蛋白沉积,且LP与HIF-1α蛋白表达呈正相关。
Objective To observe the effect of leptin (LP) on the expression of lung tissue and the fibrosis of lung in silicotic model rats and its relationship with hypoxia inducible factor 1α (HIF-1α). Methods 120 SD rats were randomly divided into normal control group, silicosis model group, LP intervention group (divided into LP5 intervention group, LP10 intervention group and LP20 intervention group according to LP concentration). Rats in control group were perfused with 1 mL of saline solution, and the other rats were intratracheally instilled with 1 mL of SiO2 suspension (40 mg / mL). One day after model establishment, LP5, LP10 and LP20 intervention groups were given 5 ng / kg · d, 10 ng / kg · d, 20 ng / kg · d LP, 6 rats were sacrificed on the 7th, 14th, 21st and 28th day. The expression of LP in the lung tissue and hydroxyproline content on the 28th day in each group were detected by ELISA. Western blot was used to detect the expression of LP and HIF-1α in lung tissue of silicosis model rats. Results The expression of LP in lung tissue of each group was significantly different at the same time (P <0.05). The expression of LP in lung tissue of the silicosis model group was significantly higher than that of the normal control group. The three different concentrations of LP intervention group were higher than the silicosis model group (P <0.05). The levels of hydroxyproline on the 28th day were (0.89 ± 0.16) mg / g, (3.14 ± 0.40) mg / g and (3.78 ± 0.40) mg / g respectively in the normal control group, silicosis model group, LP5 intervention group, LP10 intervention group and LP20 intervention group (P <0.05). The expression of LP in LP group was significantly higher than that in normal group (P <0.05). The LP expression in LP group was significantly higher than that in normal group In the silicosis model group (P <0.05). At each time point, the expression of HIF-1alpha and LP in the model group was positively correlated (r = 0.88,0.79,0.86,0.85, P <0.05). Conclusions The expression of LP in the lung tissue of silicosis model rats increased and the exogenous LP increased, which could increase the deposition of collagen in the lung tissue of silicosis rats, and there was a positive correlation between the expression of LP and HIF-1α protein.