Effect of growth hormone-releasing peptide on ardiac cholinergic nerve fiber density distribution in a rat model of heart failure

摘要

BACKGROUND: Changes in the cardiac autonomic nerve are considered to be important factors in the mechanisms of heart failure. It is possible to reduce or slow down nerve degeneration and necrosis, provided that patients take effective neuroprotectants during the early stages of heart failure. Moreover, it is possible to relieve the pathological process and reduce the risk of death.OBJECTIVE: To study the effect of growth hormone releasing peptide (GHRP) on cardiac cholinergic nerve fiber density distribution in a rat model of heart failure, and verify whether GHRP can ameliorate denervation.DESIGN, TIME AND SETTING: A randomized controlled study was performed at the Key Laboratory of Anatomy, Harbin Medical University, between June and October 2009.MATERIALS: Fifty adult, healthy, female, Wistar rats, weighing (200±20) g, were randomly divided into GHRP (n=30), model (n=10), and sham operation (n=10) groups. GHRP-2 was made in Shanghai, China (batch No. z071212-03).METHODS: Acute myocardial infarction was established by ligating the left anterior descending coronary artery in the GHRP and model groups. Five weeks later, myocardial function was detected using color ultrasound electrocardiograph. Ejection fraction < 60% was considered to be a successful marker of chronic heart failure models. However, the left anterior descending coronary artery was not ligated in the sham operation group. The GHRP group was injected with 100μg/kg GHRP-2, and the other two groups were injected with the same volume of physiological saline, once per day.MAIN OUTCOME MEASURES: After 4 weeks, pathological changes in cardiac cholinergic nerve fibers were detected under optic microscopy following hematoxylin/eosin staining. In addition, density distribution was measured using a multi-function color pathological image system.RESULTS: In the sham operation group, myocardial cells were regular, uniformly stained, and no inflammatory cells were present. In the model group, myocardial cells were unevenly stained, exhibited nuclear atrophy, degeneration, dissolution, or disappearance. In the GHRP group, myocardial damage was less than in the model group; cardiac muscle fibers exhibited slight degeneration. The myocardium in the sham operation group was serried, spreading the cholinergic innervations along the cardiac fiber. In the model group, there was a decreased number of cholinergic nerve fibers decreased, which also became shorter and smaller, compared with the sham operation group (P<0.01). In the GHRP group, cholinergic positive nerve fibers were significantly increased compared with the model group (P<0.01), but still less than the sham surgery group (P<0.05).CONCLUSION: GHRP delayed denervation and reduced nerve reconstitution following heart failure in rats.