五指山小型猪高脂血症模型的心脏自主神经功能变化

Changes of the autonomic nervous function in Wuzhishan minipig models of hyperlipidemia

目的观察五指山小型猪高脂血症模型的心脏自主神经功能的动态变化,探讨血脂异常对自主神经功能的影响和与昼夜的关系。方法利用高脂饮食诱发五指山小型猪高脂血症,造模后,每2周一次测定小型猪TG、TC、HDL-C和LDL-C和监测动态心电图,并进行24 h和昼夜心率变异性(HRV)分析,以评估小型猪的心脏自主神经功能。结果高脂饮食2周后五指山小型猪血清TC、HDL-C、LDL-C水平均显著升高(P<0.01),TG水平亦在高脂饮食后6周显著升高(P<0.05),其中,TC、LDL-C在高脂饮食0～4周时呈快速上升,在4～6周达到高峰,8～10周基本稳定并维持在一定水平;HDL-C在高脂饮食0～2周迅速上升并达到高峰,2～10周基本稳定。HRV参数分析结果,时域指标(RRI、SDNN、RMSDD、SDANN、PNN50、SDANN index、STV、LTV)和频域指标(VLF、LF、HF和TP)均渐进性显著降低(P<0.05,P<0.01),LF/HF升高(P<0.05),夜间HRV参数变化程度均高于白天;相关分析显示HRV各参数与TC、LDL-C、TC/HDL-C、LDL-C/HDL-C具有显著的相关性(P<0.05,P<0.01),经多元线性逐步回归分析发现,SDNN与TC、LDL-C、TC/HDL-C、LDL-C/HDL-C比值的相关性依次为0.673、0.672、0.665、0.681。结论高脂饮食诱发五指山小型猪高脂血症的血脂异常可引起自主神经功能的下降和紊乱,自主神经功能的紊乱程度与高血脂状态的持续时间有关;血脂异常所致心血管疾病的危险程度夜间高于白天;HRV降低与TC、LDL-C、TC/HDL-C和LDL-C/HDL-C比值升高呈一定的依赖性,SDNN降低可作为预测高脂血症引发心血管病风险的独立相关指标。

Objective The aim of this study was to observe the changes of autonomic nervous function in Wuzhishan minipigs（WZS） and investigate the relationship between dyslipidemia and 24 h or diurnal changes of autonomic nervous function in these animals.Methods The WZS minipig models of hyperlipidemia was established by feeding with high fat diet.The serum TG,TC,HDL-C and LDL-C levels were detected and electrocardiogram was monitored by non-invasion telemetry every 2 weeks.24 h or diurnal autonomic nervous function was evaluated by heart rate variability（HRV） analysis.Results The serum TC,HDL-C,LDL-C levels were significantly increased in the WZS minipigs after feeding with high fat diet for 2 weeks（P0.01）,and TG level was also significantly increased after 6 weeks（P0.05）.Among them,TC and LDL-C levels were rapidly increased during 0 to 4 weeks and reached a high peak at 4 to 6 weeks,and then maintained stable at a certain level during 8 to10 weeks.HDL-C was also rapidly increased and reached a peak during 0 to 2 weeks,and then maintained stable during 2 to 10 weeks.Meanwhile,HRV time-domain analysis indexes（including RRI,SDNN,RMSSD,SDANN,PNN50,SDANN index,STV,LTV） and HRV frequency-domain analysis indexes（including TP,VLF,LF,HF） were gradually reduced（P0.05,P0.01）,while LF/HF was significantly increased（P0.05）.The degrees of changes of the HRV parameters were slightly higher in the nighttime than those of daytime.The results of linear correlation analysis showed that there were significant correlations between TC,LDL-C,TC/HDL-C,LDL-C/HDL-C and HRV parameters（P0.05,P0.01）.Moreover,the multivariate linear gradual regressive analysis also showed that TC,LDL-C,TC/HDL-C,LDL-C/HDL-C were related with SDNN,and their correlation coefficients were 0.673,0.672,0.665 and 0.681,respectively.Conclusions Hyperlipidemia induced in WZS minipigs by high fat diet may reduce and disturb the autonomic nervous function.The degree of disturbance of autonomic nervous function may be related with duration of hyperlipidemia status,and the risk of dyslipidemia caused by cardiovascular disease is higher in the nighttime than that in daytime.There is a certain dependence between reduced HRV and increased TC,LDL-C,TC/HDL-C and LDL-C/HDL-C ratio.The reduced SDNN can be considered as a predictive indicator of hyperlipidemia independently associated with the risk of development of cardiovascular disease.