褪黑素改善内毒素血症大鼠血管反应性

观察褪黑素(melatonin,MT)对脂多糖(lipopolysaccharide,LPS)诱导的体循环和肺循环血管反应性失调的影响,并探讨可能的作用机制。实验分为溶剂对照组、LPS组、LPS+MT组和MT组。制备离体胸主动脉环和肺动脉环,应用血管张力检测技术检测各组血管环对苯肾上腺素(phenylephrine,PE)和乙酰胆碱(acetylcholine,ACh)的反应性并绘制累积剂量反应曲线;制备各组血管组织匀浆,测定丙二醛(malondialhyde,MDA)和超氧化物歧化酶(superoxidedismutes,SOD)含量变化。结果显示:与对照组相比,LPS6h后胸主动脉对PE的收缩反应减弱(P<0.01),对PE(1×10–8~1×10–5mol/L)累积剂量反应曲线下移;而肺动脉对ACh的舒张反应显著下降(P<0.01),对ACh(1×10–8~1×10–5mol/L)累积剂量反应曲线下移。加用MT可显著改善LPS诱导的胸主动脉对缩血管剂PE的低反应性,同时可逆转LPS对肺动脉舒张反应的抑制,LPS+MT组胸主动脉对PE的累积剂量反应曲线和肺动脉对ACh的累积剂量反应曲线位于对照组和LPS组之间;MT还可对抗LPS导致的脂质过氧化,使MDA含量减少,提高抗氧化酶SOD的活性。上述结果提示,MT可改善内毒素血症大鼠的血管反应性失调,抗氧化途径可能是其发挥保护作用的机制之一。

Melatonin improves vascular reactivity of endotoxemia rats

The purpose of the present study was to investigate the effect of melatonin (MT) on the abnormal reactivity of thoracic aorta and pulmonary artery induced by lipopolysaccharide (LPS) in rats. Sprague-Dawley rats were divided into four groups randomly: (1) Vehicle group; (2) LPS group: LPS (4 mg/kg, i.p.); (3) LPS+MT group: MT (5 mg/ml, i.p.) was given 30 min before LPS and 60 min after LPS (4 mg/kg ,i.p); (4) MT group: received two doses of MT, 90 min after the first injection of MT another dose of MT was given. Six hours after LPS injection,the rats were killed and both thoracic aortic rings (TARs) and pulmonary artery rings (PARs)were prepared. The reactivity of TARs and PARs in the four subgroups was tested separately. The contraction response to phenylephrine (PE) and the endothelium-dependent relaxation response (EDRR) to ACh were observed with the isolated artery ring technique. Concentration-response curves were generated with ACh or PE (1 x 10(-8) - 1 x 10(-5) mol/L). Superoxide dismutes (SOD) activity and the content of malondialhyde (MDA) in artery tissues were detected. For TARs, LPS significantly reduced the contraction response to PE compared with the vehicle group (P<0.01) and the curve of cumulative dose responses to PE in the LPS group shifted downward. Although EDRR to ACh in the LPS group had the tendency to decrease but still showed no significant difference compared with the vehicle group (P>0.05). For PARs, EDRR to ACh was depressed significantly in the LPS group (P<0.01), while no effect on contraction response to PE in the LPS group was observed, compared with the vehicle group (P> 0.05). Compared with the LPS group, TARs in the LPS+MT group exhibited an increased contraction response to PE, but were still lower than that in the vehicle group. Similarly, EDRR to ACh of PARs in the LPS+MT group was improved significantly and there was no difference between the LPS+MT group and the vehicle group. The vascular reactivity was unaffected in MT group compared with the vehicle group in both TARs and PARs. SOD activity in the LPS +MT group increased significantly and the content of MDA decreased markedly compared with the LPS group. These results suggest that MT may improve the vascular reactivity in endotoxemia rats due to its antioxidant properties.