| ObjectiveCardiac hypertrophy is an important stage in the development of cardiovascular disease. In congenital heart disease, myocardial infarction,valvular heart disease, hypertension and other cardiovascular diseases,cardiac hypertrophy is a common pathological process. The continuous stimulation from outside causes the continuous progress of cardiac hypertrophy, it also increases the myocardial oxygen consumption and reduces compliance, eventually leads to cardiac enlargement, congestive heart failure and even sudden death,so it is an independent risk factor for the increasing cardiovascular disease morbidity and mortality. With the occurrence and development of left ventricular hypertrophy, sudden death, ventricular arrhythmia, myocardial ischemia, heart failure and other cardiovascular events rate increases by6-10times. Drug treatments achieve a good effect, but the side effects and clinical effects need further verification. Intervention therapy can improve the quality of life of patients, however,as an invasive treatment technology it will inevitably have a variety of complications, such as vasovagal reflex, vascular thrombosis,chest tightness, chest pain,or even leading to death. Therefore, finding out the function mechanism of cardiac hypertrophy, treating and preventing myocardial hypertrophy positive and effective, reducing cardiovascular disease mortality and morbidity rates have become the hot spots and focuses in the field of cardiovascular research all over the world. Acupuncture, as a low-injury treatment with good effect in the prevention and treatment of heart disease, has been widely used in cl inical. Guiding by the theory of Chinese acupuncture "for heart and chest, it is point Neiguan" and on the basis of preliminary studies,with modern medical theory and experimental methods,this experiment is to study the influence of electroacupuncture "neiguan" on the p38MAPK signaling pathway in rats with cardiac hypertrophy, it has significant theoretical and practical value on the prevention and treatment of various causes of cardiac hypertrophy.MethodsA total of503-month-old female SD rats,weighing about180g, were randomly divided into five groups by random number table method:the normal group, the model group, the electroacupuncture group, the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group, with ten rats in each group respectively.The rats in the normal group received3mg/kg·d physiologic saline injection into the back skin,and rats in the model group received3mg/kg·d isoprenaline hydrochloride for14days, the ECG changes:the duration of QRS wave and QT wave extended (QRS>0.10s), considering changes of T wave morphology as a sign of successful model, the electroacupuncture group received3mg/kg.d isoprenaline hydrochloride, the acupuncture needle were penetrated5mm into the bilateral "neiguan" acupoints and interconnected with a HANS electroacupuncture apparatus, in which the following stimulus parameters were selected:continuous-wave at2Hz and1mA, for20min every day, the P38MAPK inhibitor group were injected3mg/kg·d isoprenaline hydrochloride and0.3mg/kg/d SB203580, the electroacupuncture and P38MAPK inhibitor group injected3mg/kg·d isoprenaline hydrochloride and0.3mg/kg/d SB203580, were treated with electroacupuncture for14days. On the15th day,the body weights of the rats, as well as those of their left ventricle and the whole heart were recorded; then left ventricular weight index and the heart weight index were calculated. The heart tissue was done in hematoxylin-eosin staining, the average measurement of left ventricular wall thickness, the average diameter of the myocardial cell, the myocardial fiber diameter was measured, the content of NO in heart tissue and blood plasma were determined by the method of nitric acid reductase, the content of TNF-α and IL-1β in of heart tissue and blood plasma were measured by radioimmunoassay, the immune positive expression of p38MARK and p-p38MARK were detected by immunocytochemistry method, the p38MAPK and p-p38MAPK activity were determined by western blot, then analyzed the data through image analyse system and statistical analysis system.Results1. Compared with the normal group, HW, LVW, HWI, LVWI were significantly higher with statistical significance in model group (P<0.01); compared with the model group, HW, LVW, HWI, LVWI were significantly lower with statistical significance in the electroacupuncture group,the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group (P<0.05), but no significant difference between them(P>0.05). 2. Compared with the normal group, the average measurement of left ventricular wall thickness,the average diameter of the myocardial cell, the myocardial fiber diameter were significantly higher with statistical significance in model group (P<0.01), compared with the model group, the average measurement of left ventricular wall thickness,the average diameter of the myocardial cell, the myocardial fiber diameter were significantly lower with statistical significance in the electroacupuncture group,the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group (P<0.05, p<0.01), but no significant difference between them(P>0.05).3. After staining of myocardial cells, the myocardial structure in normal group was clear, complete, uniform, and cardiac muscle fibers were arranged in neat rows, clear stripes,without morphological abnormalities;myocardial cells in model group were stained unevenly, cardiac muscle fibers was disordered, myocardial fiber diameter increased,the connective tissue among the myocardial fibers become loose,edema, hyperplasia,with the uneven size of cell,and cardiomyocyte diameter was significantly larger than that in normal group.After treatment, myocardial cells in the electroacupuncture group, the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group were slightly larger than that in model group,with acceptable arangement. Compared with the model group,cardiomyocyte hypertrophy was improved, myocardial fiber arrangement became neat, edema and hyperplasia were improved significantly.4. Compared with the normal group, the content of NO in heart tissue and blood plasma were significantly lower with statistical significance in model group (P<0.01), compared with the model group, NO in heart tissue and blood plasma were significantly higher with statistical significance in the electroacupuncture group, the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group (P<0.05),but no significant difference between them(P>0.05).5. Compared with the normal group, the content of TNF-α and IL-1β in heart tissue and blood plasma were significantly higher with statistical significance in model group (P<0.01), compared with the model group,TNF-α and IL-1β were significantly lower with statistical significance in the electroacupuncture group, the P38MAPK inhibitor group,the electroacupuncture and P38MAPK inhibitor group (P<0.05),but no significant difference between them(P>0.05).6.Compared with the normal group, the immune positive expression of p38MAPK increased, the IOD of p38MAPK and p-p38MAPK were significantly higher with statistical significance in model group (P<0.01), compared with the model group, the IOD of p38MAPK was lower with statistical significance in the electroacupuncture group, the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group (P<0.05, p<0.01), but no significant difference between them(P>0.05).7.Compared with the normal group,p38MAPK and p-p38MAPK in myocardial cells increased, was significantly higher in model group (P<0.01), compared with the model group, p38MAPK and p-p38MAPK in myocardial cells were lower with statistical significance in the electroacupuncture group, the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group (P<0.05, p< 0.01),but no significant difference between them(P>0.05).Conclusion1.Electroacupuncture at "neiguan" can decrease HWI and LVWI,the average measurement of left ventricular wall thickness, the average diameter of the myocardial cell,and the myocardial fiber diameter, and improve myocardial morphology significantly.2. Electroacupuncture at "neiguan" can increase the content of NO in heart tissue and blood plasma, and prevent the myoeardial hypertrophy by improving the content of NO.3. Electroacupuncture at "neiguan" acupoint can prevent the myoeardial hypertrophy through its anti-inflammation effect to adjust p38MAPK signaling pathway.4. P38MAPK signaling pathway is involved in myoeardial hypertrophy caused by injected with isoprenaline hydrochloride, the up-regulation of expression of p38MARK promote the probability of cardiac hypertrophy occurrence, electroacupuncture at "Neiguan" may protect cardiac hypertrophy through regulating p38MAPK signaling pathway of myocardial cell.5. There was no significant difference between the electroacu-puncture group, the P38MAPK inhibitor group, the electroacupuncture and P38MAPK inhibitor group. When electroacupuncture and P38MAPK inhibitor were added up,there was no additive effect, may be related to the strong inhibition of p38inhibitor of signaling pathways, the part effect of electroacupuncture at "Neiguan" is covered. |
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