论文部分内容阅读
目的 观察小檗碱对脂多糖所致急性肺损伤大鼠血管内皮细胞生长因子(VEGF)及其受体-2(VEGFR-2)表达的影响,探讨小檗碱对急性肺损伤的作用机制.方法 将30只Wistar大鼠随机均分为对照(Con)组、脂多糖(LPS)组和小檗碱(Ber)组,用生理盐水(0.1 mL/kg)(对照组和LPS组)或Ber(50 mg/kg)(Ber组)连续灌胃3 d后麻醉气管插管,LPS组和Ber组吸入LPS(1 mg/kg),对照组吸入等体积生理盐水.0 h、2 h、4 h、6 h时抽血行血气分析,同时进行血浆VEGF和VEGFR-2水平、肺泡灌洗液(BALF)蛋白质定量和VEGF及VEGFR-2水平、肺组织病理学、免疫组化检测.结果 Ber组和Con组2 h、4 h、6 h时间点pH和PaO2均明显高于LPS组相应时间点,PaCO2均明显低于LPS组相应时间点(均P<0.05).Ber组和Con组2 h、4 h、6 h时间点肺泡通气指数均明显低于LPS组相应时间点(P<0.05),Ber组和Con组2 h、4 h、6 h时间点BALF和血浆VEGF及VEGFR-2定量均明显高于LPS组相应时间点(均P<0.05).Ber组和Con组2 h、4 h、6 h时间点肺组织中VEGF及VEGFR-2 mRNA的表达均明显高于LP组相应时间点表达(均P0.05).结论 小檗碱能够有效预防LPS所致ALI,其作用机制可能是通过下调VEGF和VEGFR-2的表达,从而抑制VEGF的作用,保持呼吸膜的形态和功能,阻止ALI的发生.“,”Objective To observe the effects of berberine on the expression of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) during acute lung injury (ALI) and investigate the mechanism thereof. Methods 30 Wistar rats were randomly divided into 3 equal groups. The rats in the control (Con) group and lipopolysaccharide (LPS) were given normal saline (NS) 0.1 mL/kg by gavage and the rats in the berberin (Ber) group were given Bbrberine 50 mg/kg once a day for 3 days. Then all animals were anesthetized and underwent tracheal intubation, the LPS and Ber groups inhaled LPS (1 mg/kg) to cause ALI, and the control group inhaled the same amount of NS. 0h, 2h, 4h and 6h after the inhalation blood samples were collected from the left ventricle to undergo gas analysis. 6h after modeling the rats underwent bronchoalveolar lavage (BAL) with NS and collection of the BAL fluid (BALF) . Then they were killed with some lung tissue taken out to undergo pathological examination and real-time PCR to test the VEGF/VEGFR-2 mRNA. The total protein concentrations in the BALF and plasma were tested by BCA method. The pulmonarypenetration index (PVPI) was calculated. The protein concentrations of VEGF and VEGFR-2 in BALF and plasma were tested by ELISA. Results The levels of pH and PaO2 of the Ber group and Con group at 2 h、4 h、6 h were all significantly higher than those of the LPS group, and the PaCO2 level of the Ber group and Con group at 2 h、4h、6 h were all significantly lower than those of the LPS group (all P<0.05). The PVPI levels of the Ber and Con groups at 2 h, 4 h, and 6 h time points were sall ignificantly lower than those of the LPS group (all P<0.05). The VEGF and VEGFR-2 protein expression levels in the BALF and plasma of the Ber and Con groups at the 2 h, 4 h, and 6h time points were all significantly higher than those of the LPS group (all P<0.05). The mRNA expression levels of VEGF mRNA and VEGFR-2 in the lung tissues of the Ber and Con groups at the 2h, 4h, and 6h time points were all significantly lower than those of the LPS group (all P0.05). Conclusion Berberine effectively prevents ALI caused by LPS, by decreasing the VEGF and VEGFR-2 expression, thus maintaining the morphological structure and function of the respiratory membrane.