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目的探讨血管紧张素Ⅱ1型受体(AT1-R)阻断剂氯沙坦钾在全氟异丁烯(PFIB)急性肺损伤(ALI)中的防治作用。方法无特定病原体级成年雄性Wistar大鼠68只,分为17个组,每组4只。时间-效应关系研究中,设PFIB染毒前1.0、0.5 h与染毒后0.5、1.0、2.0、4.0、8.0 h氯沙坦钾干预组,并设氯沙坦钾对照组,上述8组固定氯沙坦钾给药剂量为10.00 mg/kg体质量;剂量-效应关系研究中,设氯沙坦钾给药剂量分别为1.25、2.50、5.00、10.00和15.00 mg/kg体质量的干预组,固定给药时间为染毒前1.0 h。上述2种关系研究中,均设空白对照组和PFIB染毒对照组。采用大鼠头部暴露动态吸入染毒法建立PFIB吸入性ALI模型,各干预组和PFIB染毒对照组染毒剂量均为145 mg/m3×8 min,空白对照组和氯沙坦钾对照组均行过滤空气暴露8 min。染毒后24 h处死动物,分别收集右肺组织及左肺支气管肺泡灌洗液(BALF),测定肺湿/干质量比、肺含水量、湿肺体比、干肺体比4个肺系数和BALF总蛋白水平。结果时间-效应关系研究中,PFIB染毒对照组肺湿/干质量比、肺含水量、湿肺体比3个肺系数以及BALF总蛋白水平均分别高于空白对照组、氯沙坦钾对照组(P<0.05);7个时间氯沙坦钾干预组的4个肺系数指标以及BALF总蛋白水平分别与PFIB染毒对照组比较,差异均无统计学意义(P>0.05)。剂量-效应关系研究中,PFIB染毒对照组的4个肺系数和BALF总蛋白水平均分别高于空白对照组(P<0.05);5个剂量氯沙坦钾干预组的4个肺系数以及BALF总蛋白水平分别与PFIB染毒对照组比较,差异均无统计学意义(P>0.05)。结论 AT1-R阻断剂氯沙坦钾对PFIB吸入性ALI无明显影响,提示血管紧张素Ⅱ在PFIB中毒性肺损伤中作用有限。
Objective To investigate the preventive and therapeutic effect of losartan potassium, an angiotensin Ⅱ type 1 receptor (AT1-R) blocker, on acute lung injury induced by perfluoroisobutylene (PFIB). Methods 68 adult Wistar rats without specific pathogen were divided into 17 groups with 4 rats in each group. In the study of time-effect relationship, we established losartan potassium intervention groups at 1.0,0.5 h before PFIB exposure and at 0.5, 1.0, 2.0, 4.0, 8.0 h after exposure to PFIB, and the above 8 groups were fixed Losartan potassium dose of 10.00 mg / kg body weight; dose-response relationship study, losartan potassium dose were 1.25,2.50,5.00,10.00 and 15.00 mg / kg body weight intervention group, Fixed dosing time 1.0 h before exposure. In the above two kinds of relationship studies, both blank control group and PFIB exposure control group. Inhalation ALI model of PFIB inhalation was established by dynamic inhalation exposure to the head of rats. The exposure dose of the PFIB exposure group and control group was 145 mg / m3 × 8 min. The blank control group and losartan potassium control group Air filtration was performed for 8 min. The animals were sacrificed at 24 hours after exposure and the right lung and left lung bronchoalveolar lavage fluid (BALF) were collected. The lung wet / dry weight ratio, lung water content, wet lung ratio, dry lung ratio And BALF total protein levels. Results In the study of time-effect relationship, the lung wet / dry weight ratio, lung water content, wet lung ratio and pulmonary surfactant index of BALF were higher in PFIB-treated group than those in blank control group and losartan potassium control group (P <0.05). There were no significant differences in the four indexes of pulmonary coefficient and the total protein level of BALF between the intervention group and the control group (P> 0.05). In the study of dose-effect relationship, the four pulmonary coefficients and the total BALF protein levels in the PFIB-treated control group were significantly higher than those in the blank control group (P <0.05). The four lung coefficients in the losartan-potassium intervention group The total protein level of BALF was not significantly different from that of PFIB exposure control group (P> 0.05). CONCLUSION: Losartan, an AT1-R blocker, has no effect on inhaled ALI in PFIB, suggesting that angiotensin II has a limited role in PFIB-induced lung injury.