Effect Of Propofol On Carotid Sinus Baroreceptor Reflex In Diabetic Rats

Objective: The previous study of our group found that the sensitivity of carotid sinus baroreceptor reflex(CSR)in diabetic rats was reduced,and the use of propofol would increase the inhibitory effect on CSR,indicating that intraoperative application of propofol in diabetic patients Propofol increases the incidence of cardiovascular events and increases the risk of perioperative anesthesia management.The study found that AMPA receptor GluR2 subunit and GABAA receptor are the most important excitatory neurotransmitter receptors and inhibitory neurotransmitter receptors mediating the relationship between baroreceptors and the brainstem.Phenol aggravated the relationship between CSR inhibition in diabetic rats and the AMPA receptor GluR2 subunit and GABAA receptor in the nucleus skeletal muscle,and proposed new ideas and methods for further exploration of the mechanism,in order to provide reference for clinical work.Methods: The first part: 36 male SD rats were randomly divided into three groups:control group(group N),diabetes group(group D)and AMPA receptor agonist diabetes group(group A).Each group was divided into two groups according to the different drugs:saline group(group NN,group DN and group AN),propofol group(group NP,group DP and group AP).The corresponding drugs were given according to the above groups,and then the carotid sinus area of rats was isolated and perfused with K-H solution.The changes of mean arterial pressure(map)with the rise and fall of intrasinus pressure(ISP)were observed and recorded,the ISP-MAP curve was drawn,and the CSR functional parameters were calculated.After perfusion,the brain was decapitated and the expression level of AMPA receptor GluR2 subunit in the nucleus ambiguus of each group was detected by immunoblotting and immunofluorescence.The second part: 36 male SD rats were randomly divided into two groups: control group(group N)and diabetes group(group D).Each group was divided into three groups according to the different drugs: saline group(group NN and DN),propofol group(group NP and DP),GABAA receptor antagonist +propofol group(group NPG and DPG).The corresponding drugs were given according to the above groups,and then the carotid sinus area of rats was isolated and perfused with KH solution.The changes of mean arterial pressure(map)with the rise and fall of intrasinus pressure(ISP)were observed and recorded,the ISP-MAP curve was drawn,and the CSR functional parameters were calculated.After perfusion,the brain was decapitated and the expression of GABAA receptor in the nucleus ambiguus of each group was detected by Western blot.Results: The first part: 1.CSR functional parameters:(1)Under the same femoral vein pumping drug,compared with the N group,the curve of the D group moved up,the PS and RD decreased,and the TP and SP increased.Compared with the curve of group D,the curve shifted downward,PS and RD increased,and TP and SP decreased.(2)Compared with the femoral vein pumping normal saline group(NN,DN,AN group),the curve of the pumping propofol group(NP,DP,AP group)moved up,PS and RD decreased,and TP and SP increased.Big.2.The expression levels of AMPA receptor GluR2 subunits in the nucleus skeletal nucleus were detected by Western-blot and immunofluorescence.Compared with N group(NN group,NP group),D group(DN group,DP group))The expression of AMPA receptor GluR2 subunit in the nucleus doubtful was down-regulated,while the protein expression of group A(group AN,AP)was increased compared with group D,and the difference was significant(P<0.05),and there was no difference between group N and group A Statistical significance(P>0.05).Compared with the femoral vein pumping normal saline group(NN,DN group),the femoral vein pumping propofol group(NP,DP group)down-regulated AMPA receptor GluR2 subunit expression in the nucleus doubtful(P<0.05).Compared with AP,there was no significant difference(P>0.05).The second part: 1.CSR functional parameters:(1)Compared with group N,the curve of group D moved upward,PS and RD decreased,and TP and SP increased.(2)Compared with normal saline pump group(NN,DN group),the curve of propofol pump group(NP,DP group)moved upward,PS and RD decreased,and TP and SP increased.After adding GABAA receptor inhibitor and then pumping propofol(NPG,DPG group),the curve shifted downward,PS and RD increased,and TP and SP decreased.2.Western-blot was used to detect the expression level of GABAA receptors in the nucleus doubtful.Overall,compared with the N group(NN group,NP group),the D group(DN group,DP group)nucleus doubtful.The expression of internal GABAA receptors decreased,and the difference was statistically significant(P<0.05).Compared with the femoral vein pumping normal saline group(NN group,DN group),the femoral vein pumping propofol group(NP group,DP group)increased the expression of GABAA receptors in the nucleus doubtful(P<0.05).The expression of GABAA receptors in the propofol group(NPG group and DPG group)after microinjection of Bicuculline via femoral vein was lower than that in NP and DP group(P<0.05).Conclusion: 1.Both propofol and diabetes can inhibit CSR in rats.After the application of propofol in diabetic rats,the inhibitory effect of CSR is more obvious.2.The inhibitory effect of CSR in diabetic rats is mainly related to the down-regulation of the excitatory receptor GluR2 subunit in the nucleus paraben,and the down-regulation of the inhibitory receptor GABAA receptor,resulting in the decrease of the nucleus paraben discharge.3.The inhibitory effect of propofol on CSR is mainly related to the down-regulation of the excitatory receptor GluR2 subunit and the up-regulation of the inhibitory receptor GABAA receptor in the nucleus.4.The possible mechanism of propofol aggravating the CSR inhibitory effect of diabetic rats is speculated: the nuclear discharge in diabetic rats decreases,and after propofol is administered,the excitatory receptor GluR2 subunit in the nucleus is further reduced,and the inhibitory receptor GABAA receptor greatly increased,further increasing the inhibitory effect on the nuclei of doubt,and ultimately leading to an increase in the inhibitory effect on CSR.