RESUMO
Objective:To evaluate the relationship between the mechanism of propofol inhibiting carotid sinus baroreflex (CSR) and GluR2 subunit-containing AMPA receptors in the nucleus ambiguus of rats with type 2 diabetes mellitus (T2DM).Methods:SPF healthy male Sprague-Dawley rats, aged 3 weeks, were selected and fed a high glucose and high fat diet for 6 weeks, and then streptozotocin 30 mg/kg was intraperitoneally injected to prepare a T2DM model of rats. Twenty-four T2DM rats were divided into 4 groups ( n=6 each) using a random number table method: diabetes mellitus-normal saline group (DN group), diabetes mellitus-propofol group (DP group), AMPA receptor agonist-normal saline group (AN group), and AMPA receptor agonist-propofol group (AP group). Another 12 normal rats were selected and divided into 2 groups ( n=6 each) using a random number table method: normal-normal saline group (NN group) and normal-propofol group (NP group). AMPA receptor agonist mibamitor 1 nmol/L (50 nl) was injected into the nucleus ambiguus using a micropipette at 30 min before perfusion of isolated carotid sinus in AN and AP groups. Propofol 45 mg·kg -11·h -1 was infused for 2 h via the femoral vein in NP group, DP group and AP group, and the equal volume of normal saline was given instead in the other groups. A model for perfusing isolated carotid sinus was developed at 20 min after infusion of propofol or normal saline, the intracarotid sinus pressure (ISP)-mean arterial blood pressure (MAP) curve was drawn, and CSR parameters such as maximum slope (PS), threshold pressure (TP), saturation pressure (SP), equilibrium pressure (EP), maximum decrease in MAP reflexivity (RD), and carotid sinus baroreceptor operating range (OR) were recorded. Brain tissues were taken at the end of perfusion, and the expression of GluR2 subunit in the nucleus ambiguus was detected by Western blot and immunofluorescence. Results:Compared with the corresponding normal saline groups (NN group, DN group, AN group), PS and RD were significantly decreased, TP, SP and OR were increased ( P<0.05), and the ISP-MAP curve was shifted upward in propofol groups (NP group, DP group, AP group), the expression of GluR2 subunit in the nucleus ambiguus was down-regulated in NP and DP groups ( P<0.05), and no significant change was found in the expression of GluR2 subunit in the nucleus ambiguus in AP group ( P>0.05). Compared with NP group, PS and RD were significantly decreased, TP, SP and OR were increased ( P<0.05), the ISP-MAP curve was shifted upward, and the expression of GluR2 subunit in the nucleus ambiguus was down-regulated in DP group ( P<0.05). Compared with DP group, PS and RD were significantly increased, TP, SP and OR were decreased ( P<0.05), the ISP-MAP curve was shifted downward, and the expression of GluR2 subunit in the nucleus ambiguus was up-regulated in AP group ( P<0.05). Conclusions:The mechanism by which propofol inhibits CSR may be related to down-regulation of the expression of GluR2 subunits-containing AMPA receptors in the nucleus ambiguus of rats with T2DM.