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褪黑素改善内毒素血症大鼠的血管反应性

[Melatonin improves vascular reactivity of endotoxemia rats].

作者信息

Xing Han-Ying, Ling Yi-Ling, Meng Ai-Hong, Zhao Xiao-Yun, Huang Xin-Li

机构信息

Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.

出版信息

Sheng Li Xue Bao. 2005 Jun 25;57(3):367-72.

Abstract

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.

摘要

本研究旨在探讨褪黑素(MT)对脂多糖(LPS)诱导的大鼠胸主动脉和肺动脉异常反应性的影响。将Sprague-Dawley大鼠随机分为四组:(1)溶剂对照组;(2)LPS组:腹腔注射LPS(4mg/kg);(3)LPS+MT组:在腹腔注射LPS(4mg/kg)前30分钟及注射后60分钟腹腔注射MT(5mg/ml);(4)MT组:接受两剂MT,首次注射MT 90分钟后给予另一剂MT。LPS注射6小时后,处死大鼠并制备胸主动脉环(TARs)和肺动脉环(PARs)。分别检测四个亚组中TARs和PARs的反应性。采用离体动脉环技术观察去氧肾上腺素(PE)引起的收缩反应和乙酰胆碱(ACh)引起的内皮依赖性舒张反应(EDRR)。用ACh或PE(1×10⁻⁸ - 1×10⁻⁵mol/L)绘制浓度-反应曲线。检测动脉组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。对于TARs,与溶剂对照组相比,LPS显著降低了对PE的收缩反应(P<0.01),LPS组中PE的累积剂量反应曲线下移。虽然LPS组中ACh引起的EDRR有降低趋势,但与溶剂对照组相比仍无显著差异(P>0.05)。对于PARs,LPS组中ACh引起的EDRR显著降低(P<0.01),而与溶剂对照组相比,LPS组中对PE的收缩反应未观察到影响(P>0.05)。与LPS组相比,LPS+MT组中TARs对PE的收缩反应增强,但仍低于溶剂对照组。同样,LPS+MT组中PARs对ACh的EDRR显著改善,且LPS+MT组与溶剂对照组之间无差异。与溶剂对照组相比,MT组中TARs和PARs的血管反应性均未受影响。与LPS组相比,LPS+MT组中SOD活性显著增加,MDA含量显著降低。这些结果表明,MT可能因其抗氧化特性而改善内毒素血症大鼠的血管反应性。

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