Effect of non-genomic actions of thyroid hormones on the anaesthetic effect of propofol

摘要

Hyperthyroidism is a common disease of the endocrine system and it is known that additional propofol anaesthesia is required during surgery for patients with hyperthyroidism compared with those with normal thyroid function. The aim of the present study was to determine the mechanism through which thyroid hormones (THs) inhibit the effect of propofol anaesthesia. Immunofluorescence techniques were used to verify the difference between the expression quantities of gamma-aminobutyric acid type A (GABAA) receptor subunits alpha 2 and beta 2 in the dorsal root ganglions (DRGs) of rats with hyperthyroidism and those in normal rats. Perforated patch clamp recordings in the whole-cell mode were performed to detect the GABA-activated current in acutely isolated rat DRG neurons from rats with hyperthyroidism and normal rats. This method was also used to evaluate the change in the GABA-activated currents following the pre-perfusion of propofol with and without 3,3', 5-L-triiodothyronine (T3). Compared with normal rats, rats with hyperthyroidism expressed same quantities of GABAA receptor alpha 2 and beta 2 subunits in DRGs. In addition, no difference in GABA-activated currents in the acutely isolated DRG neurons from the two types of rat was observed (P>0.05). T3 inhibits or minimises the augmentation effect of propofol on the GABA-activated currents (P<0.05). The inhibitory effect of T3 on propofol was minimised by increasing the propofol concentration (P<0.05). The inhibitory effect of T3 on the anaesthetic effect of propofol is achieved through the inhibition of the function of GABAA receptors through the non-genomic actions of the THs, rather than by changing the number of GABAA receptors. This inhibitory effect can be mitigated by increasing the propofol concentration. In conclusion, rats with hyperthyroidism require a larger dose of propofol to induce anaesthesia since the non-genomic actions of THs suppress GABA receptors, which in turn inhibits the anaesthetic action of propofol.