下丘脑室旁核在电针内关穴抗家兔急性心肌缺血作用中的机制研究
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摘要
目的 探讨经穴-脏腑相关是揭示经络实质和针灸作用机制的关键性研究方向之一。我们选择内关穴治疗缺血性心脏病——这一已经千百年临床和数十年实验研究证实疗效的针治方法为研究内容，在既往研究的基础上，观察针刺内关穴对急性心肌缺血家兔心电图、缺血心室肌细胞单相动作电位、缺血心肌超微结构的影响，研究下丘脑室旁核在内关-心脏相关中枢途径中的作用，并对参与其中的可能有效神经活性物质以及可能的效应通路进行探讨，以期从神经—内分泌—免疫网络角度为探讨电针内关穴抗家兔急性心肌缺血损伤的中枢机制提供依据。
方法 采用左冠状动脉前降支结扎法制备家兔急性心肌缺血模型，观察电针内关穴对心电图ST段电位、缺血心肌细胞单相动作电位幅度与时程、缺血心肌超微结构、下丘脑室旁核内白细胞介素-1、β-内啡肽表达的影响；并分别进行下丘脑室旁核电解预损毁、下丘脑室旁核内预微量注射阿片受体拮抗剂纳络酮、脊髓C_6～T_5节段蛛网膜下腔预注射特异性精氨酸加压素受体拮抗剂各项预处理，观察各项预处理对电针内关穴效应的影响。
结果 1．电针内关穴能显著降低实验性急性心肌缺血家兔心电图ST电位、抑制其心室肌细胞单相动作电位幅度衰减、缩短心室肌细胞单相动作电位时程、改善心肌超微结构(P＜0.05)，其中，缺血前15min预针刺组显著优于缺血即刻电针组(P＜0.05)；
2．下丘脑室旁核电解损毁导致家兔出现一过性轻度心肌缺血，下丘脑室旁核电解损毁显著降低电针内关穴抗急性心肌缺血损伤效应(p＜0.05)；
3．下丘脑室旁核微量注射纳络酮对家兔心脏功能无显著影响；下丘脑室旁核微量注射显著降低电针内关穴抗急性心肌缺血损伤效应(p＜0.05)；
4．脊髓C_6～T_5节段蛛网膜下腔注射特异性精氨酸加压素受体拮抗剂对家兔心脏功能无显著影响；脊髓C_6～T_5节段蛛网膜下腔注射特异性AVP受体拮抗剂显著降低电针内关穴抗急性心肌缺血损伤效应(p＜0.05)。
结论 1．电针内关穴能显著降低实验性急性心肌缺血家兔心电图ST电位、抑制其心室肌细胞单相动作电位幅度衰减、缩短心室肌细胞单相动作电位时程、改善心肌超微结构，从而改善急性缺血状况、抗急性缺血损伤；其中预先电针治疗疗效更佳；
2．下丘脑室旁核参与内关—心脏相关的中枢通路，损毁室旁核会在一定程度上显著降低电针内关穴抗急性心肌缺血的效应；
3．下丘脑室旁核区的β-内啡肽与白细胞介素-1参与电针内关穴抗急性心肌缺血损伤的效应；
4．下丘脑室旁核—脊髓的精氨酸加压素能直接下行通路是电针内关穴抗急性心肌缺血损伤的效应途径之一；
下丘脑室旁核可能通过神经免疫调节的多环节参与电针内关穴抗急性心肌缺血损伤的作用。
Objective The incidence between acupoint and viscera is one of the most significant orientantion in the research on the essence of meridion. To proffer evidence to the study on the mechanism of electacupuncture on Neiguan curing AMI, the theme "stimulate on Neiguan acupoint can cure hear disease"which was verifed by massive clinic and study was chosen as the study content, the effect on MII by electacupuncture on Neiguan was observed, to quest the function of PVN and probe in the probable effector substance and the tract.
Method After the ligation of the coronary artery,the effect of electricacupuncture on Neiguan including ST potential of ECG,the expression of interleukin -1 and β-endorphine in PVN and the monophasic action potential.the monophasic action potential durations and ultrastructure in the ischemial region is observed.Further more,the diversification of the effect after the electrolytic lesion on PVN or the microinjection NLX into PVN or the intrathecal injection AVPX in the C6 - T5 spinal segments were respectivly observed.
Result 1.electricacupuncture on Neiguan can evidently reduce the preternatural increase of ST potential of ECG, the monophasic action potential and the monophasic action potential durations and meliorate the ultrastructure occuring after the ligation(p<0.05),and electricacupuncture 15 minite before the ligation is more effective than electricacupuncture just begining with the ligation(p<0.05);
2. the electrolytic lesion on PVN causes temporarily slight AMI and can inhibit the effect of electricacupuncture obviously(p<0.05);
3.the microinjection NLX into PVN evidently reduces the effect of electricacupuncture as soon as nearly no detective effect on the function of the normal rabbit heart;
4.the intrathecal injection AVPX in the C6 - T5 spinal segments evidently reduces the effect of electricacupuncture as soon as nearly no detective effect on the function of the normal rabbit heart;
Conclusion 1. electricacupuncture on Neiguan can signifisantly attennuate the MII,and electricacupuncture in advence is more effective ;
2.PVN involed in the CNS thorough fare of the incidence between Neiguan and the heart;
3. β -endorphine and interleukin -1 in PVN are active in the mechanism of electricacupuncture on Neiguan attenuating the MII;
4. PVN-spinal Avp-ergic pathway is one of the probable efferent pathway in the machanism of electricacupuncture on Neiguan attenuating the MII;
PVN takes an important role in the machanism of electricacupuncture on Neiguan attenuating the MII through numerous link of neuroimmunomodulation.
方法 采用左冠状动脉前降支结扎法制备家兔急性心肌缺血模型，观察电针内关穴对心电图ST段电位、缺血心肌细胞单相动作电位幅度与时程、缺血心肌超微结构、下丘脑室旁核内白细胞介素-1、β-内啡肽表达的影响；并分别进行下丘脑室旁核电解预损毁、下丘脑室旁核内预微量注射阿片受体拮抗剂纳络酮、脊髓C_6～T_5节段蛛网膜下腔预注射特异性精氨酸加压素受体拮抗剂各项预处理，观察各项预处理对电针内关穴效应的影响。
结果 1．电针内关穴能显著降低实验性急性心肌缺血家兔心电图ST电位、抑制其心室肌细胞单相动作电位幅度衰减、缩短心室肌细胞单相动作电位时程、改善心肌超微结构(P＜0.05)，其中，缺血前15min预针刺组显著优于缺血即刻电针组(P＜0.05)；
2．下丘脑室旁核电解损毁导致家兔出现一过性轻度心肌缺血，下丘脑室旁核电解损毁显著降低电针内关穴抗急性心肌缺血损伤效应(p＜0.05)；
3．下丘脑室旁核微量注射纳络酮对家兔心脏功能无显著影响；下丘脑室旁核微量注射显著降低电针内关穴抗急性心肌缺血损伤效应(p＜0.05)；
4．脊髓C_6～T_5节段蛛网膜下腔注射特异性精氨酸加压素受体拮抗剂对家兔心脏功能无显著影响；脊髓C_6～T_5节段蛛网膜下腔注射特异性AVP受体拮抗剂显著降低电针内关穴抗急性心肌缺血损伤效应(p＜0.05)。
结论 1．电针内关穴能显著降低实验性急性心肌缺血家兔心电图ST电位、抑制其心室肌细胞单相动作电位幅度衰减、缩短心室肌细胞单相动作电位时程、改善心肌超微结构，从而改善急性缺血状况、抗急性缺血损伤；其中预先电针治疗疗效更佳；
2．下丘脑室旁核参与内关—心脏相关的中枢通路，损毁室旁核会在一定程度上显著降低电针内关穴抗急性心肌缺血的效应；
3．下丘脑室旁核区的β-内啡肽与白细胞介素-1参与电针内关穴抗急性心肌缺血损伤的效应；
4．下丘脑室旁核—脊髓的精氨酸加压素能直接下行通路是电针内关穴抗急性心肌缺血损伤的效应途径之一；
下丘脑室旁核可能通过神经免疫调节的多环节参与电针内关穴抗急性心肌缺血损伤的作用。
Objective The incidence between acupoint and viscera is one of the most significant orientantion in the research on the essence of meridion. To proffer evidence to the study on the mechanism of electacupuncture on Neiguan curing AMI, the theme "stimulate on Neiguan acupoint can cure hear disease"which was verifed by massive clinic and study was chosen as the study content, the effect on MII by electacupuncture on Neiguan was observed, to quest the function of PVN and probe in the probable effector substance and the tract.
Method After the ligation of the coronary artery,the effect of electricacupuncture on Neiguan including ST potential of ECG,the expression of interleukin -1 and β-endorphine in PVN and the monophasic action potential.the monophasic action potential durations and ultrastructure in the ischemial region is observed.Further more,the diversification of the effect after the electrolytic lesion on PVN or the microinjection NLX into PVN or the intrathecal injection AVPX in the C6 - T5 spinal segments were respectivly observed.
Result 1.electricacupuncture on Neiguan can evidently reduce the preternatural increase of ST potential of ECG, the monophasic action potential and the monophasic action potential durations and meliorate the ultrastructure occuring after the ligation(p<0.05),and electricacupuncture 15 minite before the ligation is more effective than electricacupuncture just begining with the ligation(p<0.05);
2. the electrolytic lesion on PVN causes temporarily slight AMI and can inhibit the effect of electricacupuncture obviously(p<0.05);
3.the microinjection NLX into PVN evidently reduces the effect of electricacupuncture as soon as nearly no detective effect on the function of the normal rabbit heart;
4.the intrathecal injection AVPX in the C6 - T5 spinal segments evidently reduces the effect of electricacupuncture as soon as nearly no detective effect on the function of the normal rabbit heart;
Conclusion 1. electricacupuncture on Neiguan can signifisantly attennuate the MII,and electricacupuncture in advence is more effective ;
2.PVN involed in the CNS thorough fare of the incidence between Neiguan and the heart;
3. β -endorphine and interleukin -1 in PVN are active in the mechanism of electricacupuncture on Neiguan attenuating the MII;
4. PVN-spinal Avp-ergic pathway is one of the probable efferent pathway in the machanism of electricacupuncture on Neiguan attenuating the MII;
PVN takes an important role in the machanism of electricacupuncture on Neiguan attenuating the MII through numerous link of neuroimmunomodulation.
引文
[1] 朱志茹．心肌缺血情况下心肌动作电位仿真研究．北京生物医学工程，2003，22(3)：196．
[2] Franz MR., Flaherty JT., Platia EV., et al. Indicatization of regional myocardial ischemia by recording of monophasic action potential.Circulation, 1984, 1, 9(3): 59.
[3] John-RM.,Taggart-PI. Endocardial monophasic action potential recordings for the detection of myocardial ischemia in man: a study using atrial pacing stress and myocardial perfusion scintgraphy. Am Heart J. 1991,122(6): 1599.
[4] Mohabir R.,Franz MR..In vivo electrophysiological detection of mycardia ischemia through monophasic action potential recording. Prog-cardiovasc-dis. 1991, 34(1): 15.28.
[5] 魏广和．家兔急性心肌缺血对心室复极离散度影响的研究，苏州医学院学报 1998，18(10)：1013．
[6] Jennings RB., Hawkin HK., Lowe JE., et al. Relation between high energy phosphate andlethal injury inmyocardial ischemiain the dog.Am J Pathol, 1978, 92(1):187.
[7] Foreman RD., Hancock MB., et al. Responses of spinothalamic tract cells in the thoracic spinal cord of the monkey to cutaneous and visceral inputs. Pain. 1981, 11: 149-162.
[2] Franz MR., Flaherty JT., Platia EV., et al. Indicatization of regional myocardial ischemia by recording of monophasic action potential.Circulation, 1984, 1, 9(3): 59.
[3] John-RM.,Taggart-PI. Endocardial monophasic action potential recordings for the detection of myocardial ischemia in man: a study using atrial pacing stress and myocardial perfusion scintgraphy. Am Heart J. 1991,122(6): 1599.
[4] Mohabir R.,Franz MR..In vivo electrophysiological detection of mycardia ischemia through monophasic action potential recording. Prog-cardiovasc-dis. 1991, 34(1): 15.28.
[5] 魏广和．家兔急性心肌缺血对心室复极离散度影响的研究，苏州医学院学报 1998，18(10)：1013．
[6] Jennings RB., Hawkin HK., Lowe JE., et al. Relation between high energy phosphate andlethal injury inmyocardial ischemiain the dog.Am J Pathol, 1978, 92(1):187.
[7] Foreman RD., Hancock MB., et al. Responses of spinothalamic tract cells in the thoracic spinal cord of the monkey to cutaneous and visceral inputs. Pain. 1981, 11: 149-162.