重症中暑对大鼠心肌肾素-血管紧张素系统的影响

Effect of severe heatstroke on local cardiac renin angiotensin system in rats

目的探讨重症中暑对大鼠心肌肾素-血管紧张素系统的影响。方法选用雄性Wistar大鼠24只,应用随机数表法将大鼠分为正常对照组、热打击后2 h组、热打击后24 h组,每组8只。采用放射免疫法测定大鼠血浆和心肌肾素及血管紧张素Ⅱ活性,采用免疫组化法测定心肌血管紧张素Ⅱ-1、2型受体(AT1R、AT2R)蛋白表达水平。结果大鼠热打击后60 min左右肛温达到42℃,77 min左右平均动脉压下降25 mm Hg,此时即重症中暑造模成功。热打击后2 h及24 h组大鼠血浆和心肌肾素-血管紧张素系统显著激活[血浆RA:(2 237.0±173.2)、(1 498.0±172.3)vs(785.4±43.2),P<0.05;血浆AngⅡ:(143.4±19.8)、(76.8±21.6)vs(42.8±8.6),P<0.05;心肌RA:(10.63±0.59)、(8.49±0.92)vs(1.66±0.38)P<0.05;心肌AngⅡ:(279.9±11.3)、(212.5±10.1)vs(39.6±6.3)P<0.05];热打击后24 h组大鼠血浆和心肌肾素-血管紧张素系统仍处于激活水平,但较热打击后2 h组明显下降[血浆RA:(2237.0±173.2)vs(1498.0±172.3),P<0.05;血浆AngⅡ:(143.4±19.8)vs(76.8±21.6),P<0.05;心肌RA:(10.63±0.59)vs(8.49±0.92),P<0.05;心肌AngⅡ:(79.9±11.3)vs(212.5±10.1),P<0.05]。热打击后2 h及24 h组心肌AT1R蛋白表达明显上调[(49.8±14.1)、(52.6±15.8)vs(13.0±5.0),P<0.05];热打击对AT2R蛋白表达无影响[(14.1±6.2)、(16.8±7.3)vs(9.8±4.5),P>0.05]。结论重症中暑早期能够导致大鼠心肌肾素-血管紧张素系统显著激活。

Objective To investigate the effects of severe heatstroke on rat cardiac renin angiotensin system(RAS). Methods A total of 24 male Wistar rats were randomly divided into control group, 2 hours after severe heatstroke group and 24 hours after severe heatstroke group, with 8 rats in each group. Renin activity(RA) and angiotensinⅡ(AngⅡ) in plasma and myocardium were determined with radioimmunoassay. Cardiac angiotensin Ⅱ type 1, 2 receptor(AT1R, AT2R) protein levels were examined by immunohistochemical method. Results After 60 minutes of heatstroke, rectal core temperature of rats reached 42℃ or above, and mean arterial pressure decreased to 25 mm Hg after 77 minutes. When these conditions meet the requirements, the severe heatstroke model was successfully established. Compared with control group, 2 and 24 hours after heat stroke groups had significantly higher RA and Ang Ⅱ in plasma and myocardium [plasma RA:(2237.0±173.2),(1498.0±172.3) vs(785.4±43.2), P<0.05; plasma AngⅡ:(143.4±19.8),(76.8±21.6) vs(42.8 ± 8.6), P<0.05; myocardium RA:(10.63 ± 0.59),(8.49 ± 0.92) vs(1.66 ± 0.38), P<0.05; myocardium Ang Ⅱ:(279.9 ± 11.3),(212.5 ± 10.1) vs(39.6 ± 6.3) P<0.05]; Compared with 2 hours after heat stroke groups, 24 hours after heat stroke groups had significantly lower RA and AngⅡ in plasma and myocardium [plasma RA:(2 237.0±173.2) vs(1 498.0±172.3), P<0.05; plasma AngⅡ:(143.4±19.8) vs(76.8±21.6), P<0.05; myocardium RA:(10.63±0.59) vs(8.49±0.92), P<0.05; myocardium AngⅡ:(279.9±11.3) vs(212.5±10.1), P<0.05]. Compared with control group, AT1 R protein levels notably increased in 2 and 24 hours after heat stroke groups [(49.8±14.1),(52.6±15.8) vs(13.0±5.0), P<0.05]. No apparent changes were observed in AT2 R protein level [(14.1±6.2),(16.8±7.3) vs(9.8±4.5), P>0.05]. Conclusion Heat stroke can significantly activate renin angiotensin system in both plasma and myocardium in rats in the early stage.