高胸段硬膜外交感神经阻滞对慢性心力衰竭大鼠冠状动脉微循环的影响

Effect of high thoracic segment epidural sympathetic nerve block on coronary microcirculation in rats with chronic heart failure

目的评估高胸段硬膜外交感神经阻滞(HTSB)治疗对慢性心力衰竭(CHF)大鼠冠状动脉微循环的影响。方法2023年6~9月在宁德师范学院将30只雄性Wistar大鼠根据随机数字表法随机分为对照组、CHF组和HTSB组每组10只。通过皮下注射异丙肾上腺素(ISO)来建立CHF大鼠模型。通过硬膜外导管注射0.2%罗哌卡因进行HTSB治疗。测定冠状动脉血流速度储备(CFVR)、射血分数(EF)、缩短分数(FS)、舒张末期左心室内径(LVDd)和收缩末左心室内径(LVDs)。采用相应试剂盒检测血清一氧化氮(NO)、肌酸激酶(CK)、丙二醛(MDA)、超氧化物歧化酶(SOD)、N末端B型利钠肽原(NT-proBNP)、肿瘤坏死因子-α(TNF‐α)、白介素-6(IL-6)水平。蛋白免疫印迹分析相关蛋白表达。结果与对照组相比,CHF组大鼠CFVR、EF和FS显著降低[(3.27±0.61)比(2.51±0.65),(78.35±0.25)%比(53.58±6.75)%,(38.22±4.69)%比(24.37±3.18)%,P<0.05];与CHF组相比,HTSB组大鼠CFVR、LVDd和显著升高(P<0.05)。与对照组相比,CHF组大鼠血清CK、cTnI、NT-proBNP、TNF-α、IL-6和MDA水平均显著升高,而NO、SOD水平显著降低(P<0.05);与CHF组相比,HTSB组大鼠血清CK、cTnI、NT-proBNP、TNF-α、IL-6和MDA水平均显著降低,而NO、SOD水平显著升高(P<0.05)。与对照组相比,HTSB组大鼠心肌组织诱导型一氧化氮合酶(iNOS)、细胞间黏附分子-1(ICAM-1)和P-选择素(P-Selectin)表达均显著升高,而内皮型一氧化氮合酶(eNOS)表达显著降低(P<0.05);与CHF组相比,HTSB组大鼠iNOS、ICAM-1和P-Selectin表达均显著降低,而eNOS表达显著升高(P<0.05)。结论HSTB治疗能够改善CHF大鼠冠状动脉微循环功能障碍,这可能是通过抑制炎症反应和氧化应激进而减轻内皮功能障碍来实现。

Objective To evaluate the effect of high thoracic segment epidural sympathetic nerve block(HTSB)treatment on coronary microcirculation in rats with chronic heart failure(CHF).Method Thirty male Wistar rats were randomly divided into the control,CHF and HTSB groups at Ningde Teachers College from June to September 2023,10 rats in each group according to the random number table method.The CHF rat model was established by subcutaneous injection of isoprenaline(ISO).HTSB was performed by injecting 0.2%ropivacaine through an epidural catheter.Coronary flow velocity reserve(CFVR),ejection fraction(EF),shortening fraction(FS),end-diastolic left ventricular internal diameter(LVDd)and end-systolic left ventricular internal diameters(LVDs)were measured.Serum nitric oxide(NO),creatine kinase(CK),malondialdehyde(MDA),superoxide dismutase(SOD),N-terminal pro-B-type natriuretic peptide(NT-proBNP),tumor necrosis factor-alpha(TNF-α),and interleukin-6 were detected using the corresponding kits.Western blot was performed to analyze the expression of relevant proteins.Results Compared to the control group,CFVR,EF and FS were significantly lower in rats in the CHF group[(3.27±0.61)vs.(2.51±0.65),(78.35±0.25)%vs.(53.58±6.75)%,(38.22±4.69)%vs.(24.37±3.18)%,P<0.05];compared to the CHF group,CFVR,LVDd and LVDs were significantly higher in rats in the HTSB group(P<0.05).Compared with the control group,serum CK,cTnI,NT-proBNP,TNF-α,IL-6 and MDA levels were significantly higher,while NO and SOD levels were significantly lower in rats in the CHF group(P<0.05);compared with the CHF group,serum CK,cTnI,NT-proBNP,TNF-α,IL-6 and MDA levels were significantly lower,while NO and SOD levels were significantly higher in the HTSB group of rats(P<0.05).Compared with the control group,the expression of inducible nitric oxide synthase(iNOS),intercellular adhesion molecule-1(ICAM-1)and P-Selectin were significantly elevated,while the expression of endothelial nitric oxide synthase(eNOS)was significantly reduced in the myocardial tissues of rats in the HTSB group(P<0.05);compared with the CHF group,the expression of iNOS,ICAM-1 and P-Selectin were all significantly lower,while the expression of eNOS was significantly higher in the HTSB group of rats(P<0.05).Conclusion HSTB treatment would improve coronary microcirculatory dysfunction in CHF rats,which may be achieved by inhibiting inflammatory response and oxidative stress,thus attenuating endothelial dysfunction.