雷公藤甲素对内毒血症大鼠血管低反应性的影响
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摘要
目的探讨雷公藤甲素(triptolide,TP)对内毒血症大鼠模型血液流变性及血管张力的影响。方法将雄性SD大鼠随机分成6组:正常组(NC组)、内毒血症模型组(LPS组)、TP低浓度干预组(LPS+TP-L组)、TP中浓度干预组(LPS+TP-M组)、TP高浓度干预组(LPS+TP-H组)和多黏菌素B组(LPS+PMX-B组)。用LPS 10 mg/kg腹腔注射处理6 h复制内毒血症大鼠模型。TP干预组在大鼠腹腔注射LPS前15 min进行预处理。各组行颈总动脉插管测量血流动力学指标,取胸主动脉环测定其张力变化。结果与NC组比较,LPS组大鼠血流动力学指标[心率(heart rate,HR)、平均动脉压(mean arterial blood pressure,MABP)、左室舒张压(left ventricular diastolic pressure,LVDP)、左心室内压最大上升/下降速率(maximal rate of the increase/decrease of left ventricular pressure,±dp/dt_(max))]均显著下降(P<0.05);LPS组主动脉环对10~(-8)～10~(-5) mol/L去氧肾上腺素(phenylephrine,Phe)的收缩率明显降低,对乙酰胆碱的舒张率亦明显降低(P<0.05);与LPS组比较,TP干预组各项指标均明显改善(P<0.05);而TP干预去内皮血管环组对10~(-8)～10~(-5) mol/L Phe引起的收缩率变化无统计学意义(P>0.05);经非选择性一氧化氮合酶抑制剂左旋硝基精氨酸甲酯或腺苷酸环化酶抑制剂亚甲蓝预处理后,各组内皮完整血管环对Phe的收缩率均明显改善(P<0.05)。结论 TP改善内毒血症大鼠血管低反应性与其改善内皮功能有关。
Objective To investigate the effect of triptolide(TP)on hemorrheology and vascular tension in a rat model of toxicemia.Methods Male Sprague-Dawley rats were randomly divided into normal control group(NC group),toxicemia model group[lipopolysaccharide(LPS)group],low-dose TP group(LPS+TP-L group),middle-dose TP group(LPS+TP-M group),high-dose TP group(LPS+TP-H group),and polymyxin B group(LPS+PMX-B group).The rats were intraperitoneally injected with LPS 10 mg/kg for 6 hours to establish a model of toxicemia.The TP intervention groups were given pretreatment at 15 minutes before intraperitoneal injection of LPS.Common carotid artery intubation was performed to measure hemodynamic parameters,and the change in the tension of the thoracic aortic ring was measured.Results Compared with the NC group,the LPS group had significant reductions in heart rate,mean arterial blood pressure,left ventricular diastolic pressure,and maximal rate of the increase/decrease of left ventricular pressure(P<0.05),as well as significant reductions in the rate of contraction of the aortic ring induced by 10-8-10-5 mol/L phenylephrine and the rate of dilation of the aortic ring induced by acetylcholine(P<0.05).Compared with the LPS group,the TP intervention groups had significant improvements in the above indices(P<0.05).The TP intervention group with endothelium-denuded aortic ring had no significant change in the systolic rate due to 10-8-10-5 mol/L phenylephrine(P>0.05);after the treatment with L-nitro-arginine methyl ester(a non-selective nitric oxide synthase inhibitor)or methylene blue(an adenylyl cyclase inhibitor),each group had a significant improvement in contraction of the aortic ring with intact endothelium induced by phenylephrine(P<0.05).Conclusion TP can improve vascular hyporeactivity in rats with toxicemia,possibly by improving endothelial function.
Objective To investigate the effect of triptolide(TP)on hemorrheology and vascular tension in a rat model of toxicemia.Methods Male Sprague-Dawley rats were randomly divided into normal control group(NC group),toxicemia model group[lipopolysaccharide(LPS)group],low-dose TP group(LPS+TP-L group),middle-dose TP group(LPS+TP-M group),high-dose TP group(LPS+TP-H group),and polymyxin B group(LPS+PMX-B group).The rats were intraperitoneally injected with LPS 10 mg/kg for 6 hours to establish a model of toxicemia.The TP intervention groups were given pretreatment at 15 minutes before intraperitoneal injection of LPS.Common carotid artery intubation was performed to measure hemodynamic parameters,and the change in the tension of the thoracic aortic ring was measured.Results Compared with the NC group,the LPS group had significant reductions in heart rate,mean arterial blood pressure,left ventricular diastolic pressure,and maximal rate of the increase/decrease of left ventricular pressure(P<0.05),as well as significant reductions in the rate of contraction of the aortic ring induced by 10-8-10-5 mol/L phenylephrine and the rate of dilation of the aortic ring induced by acetylcholine(P<0.05).Compared with the LPS group,the TP intervention groups had significant improvements in the above indices(P<0.05).The TP intervention group with endothelium-denuded aortic ring had no significant change in the systolic rate due to 10-8-10-5 mol/L phenylephrine(P>0.05);after the treatment with L-nitro-arginine methyl ester(a non-selective nitric oxide synthase inhibitor)or methylene blue(an adenylyl cyclase inhibitor),each group had a significant improvement in contraction of the aortic ring with intact endothelium induced by phenylephrine(P<0.05).Conclusion TP can improve vascular hyporeactivity in rats with toxicemia,possibly by improving endothelial function.
引文
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[2] LIMA S S C P,MARRA A R,DUR O M S,et al.Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting[J].PloS One,2011,6(11):e26790.
[3] CRUZ D N,PERAZELLA M A,BELLOMO R,et al.Effectiveness of polymyxin B-immobilized fiber column in sepsis:a systematic review[J].Critical care,2007,11(2):R47.
[4] 李永桂,杨正根,曾萍,等.内毒素血症的发病机制及治疗研究进展[J].广东化工,2016,43(11):143-144.
[5] LIU Q.Triptolide and its expanding multiple pharmacological functions[J].International immunopharmacology,2011,11(3):377-383.
[6] WEI D,HUANG Z.Anti-inflammatory effects of triptolide in LPS-induced acute lung injury in mice[J].Inflammation,2014,37(4):1307-1316.
[7] LIANG Z,LEO S,WEN H,et al.Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats[J/OL].BMC Cardiovasc Disord,2015,15:42[2015-05-13].https://www.ncbi.nlm.nih.gov/pmc/articles/PMC44314 61.DOI:10.1186/s12872-015-0030-4.
[8] 王海华,闵志雪,戚仁斌,等.iNOS-GC-cGMP信号活化参与了内毒素血症大鼠血管低反应性的发生机制[J].中国病理生理杂志,2012,28(6):1076-1081.
[9] FLEISCHMANN C,SCHERAG A,ADHIKARI N K,et al.Assessment of global incidence and mortality of hospital-treated sepsis.Current estimates and limitations[J].Am J Respir Crit Care Med,2016,193(3):259-272.
[10] CAWCUTT K A,PETERS S G.Severe sepsis and septic shock:clinical overview and update on management [J].Mayo Clinic proceedings,2014,89(11):1572-1578.
[11] 张倩,彭广操,朱明军.雷公藤的药理作用及毒性研究进展[J].中西医结合心脑血管病杂志,2016,14(15):1753-1754.
[12] TANAKA Y,KOIKE K,TORO L.MaxiK channel roles in blood vessel relaxations induced by endothelium-derived relaxing factors and their molecular mechanisms[J].J Smooth Muscle Res,2005,40(4-5):125.
[13] KORKMAZ B,BUHARALIOGLU K,SAHANFIRAT S,et al.Activation of MEK1/ERK1/2/iNOS/sGC/PKG pathway associated with peroxynitrite formation contributes to hypotension and vascular hyporeactivity in endotoxemic rats[J].Nitric Oxide,2011,24(3):160-172.