Effect of Guizhi Decoction ([symbols; see text]) on heart rate variability and regulation of cardiac autonomic nervous imbalance in diabetes mellitus rats

Chin J Integr Med. 2014 Jul;20(7):524-33. doi: 10.1007/s11655-014-1861-z. Epub 2014 Jun 28.


Objective: To observe abnormalities in heart rate variability (HRV) in diabetic rats and to explore the effects of treatment with Guizhi Decoction ([symbols; see text]) on cardiac autonomic nervous (CAN) imbalance.

Methods: A radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures: standard deviation of all RR intervals in 24 h (SDNN), root mean square of successive differences (RMSSD), percentage of differences between adjacent RR intervals greater than 50 ms (PNN50), and standard deviation of the averages of RR intervals (SDANN); frequency domain measures: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin (STZ)-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 (GAP-43), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) levels using an enzyme-linked immunosorbent assay.

Results: (1) STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. (2) Compared with the model group, only RMSSD and TP increased in the methycobal group significantly (P<0.05); SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased (P<0.05), and SDANN just showed a decreasing trend in the Guizhi Decoction group (P>0.05). TH increased, CHAT decreased, and TH/CHAT increased in the myocardial homogenate of the model group (P<0.05). Compared with the model group, left ventricular TH reduced in the methycobal group; and in the Guizhi Decoction group CHAT increased, while TH and TH/CHAT decreased (P<0.05). Compared with the model group, CNTF in the interventricular septum increased in the methycobal group (P<0.05); GAP-43 increased, NGF decreased, and CNTF increased (P<0.05) in the Guizhi Decoction group. There were significant differences in the reduction of NGF and elevation of CNTF between the Guizhi Decoction group and the methycobal group (P<0.05). (3) Immunohistochemical results showed that TH expression significantly increased and CHAT expression significantly decreased in the myocardia of the model group, whereas TH expression decreased and CHAT expression increased in the Guizhi Decoction group (P<0.05).

Conclusion: Guizhi Decoction was effective in improving the function of the vagus nerve, and it could alleviate autonomic nerve damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autonomic Nervous System / drug effects*
  • Autonomic Nervous System / physiopathology
  • Choline O-Acetyltransferase / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetic Neuropathies / drug therapy
  • Diabetic Neuropathies / physiopathology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Heart / innervation*
  • Heart / physiopathology
  • Heart Rate / drug effects*
  • Heart Rate / physiology
  • Male
  • Monitoring, Physiologic / methods
  • Rats, Wistar
  • Telemetry / methods
  • Treatment Outcome
  • Tyrosine 3-Monooxygenase / metabolism
  • Vagus Nerve / drug effects*
  • Vagus Nerve / physiopathology


  • Drugs, Chinese Herbal
  • guizhi decoction
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase