Progesterone Affects The Vagus Nerve Regulation Mechanism Of Duodenal Myoelectric Activity In Rabbits

Progesterone(P)is a sex steroid hormone secreted by luteal cells and plays an important role in the reproductive function of females such as pregnancy and childbirth.Studies have shown that P participates in the regulation of emotion,cognition,neurodegeneration,neuroprotection and nerve regeneration through the action of the nervous system.It is shown that P plays a major role in the inhibition of neurotoxicity.The Dorsal Motor nucleus of the Vagus(DMV)is one of the last pathways for the central nervous system to regulate gastrointestinal motility as a nucleus that receives the superior neurological central control and plays a dominant role in visceral activity.Glutamate nerve fibers from the solitary tract nucleus and the advanced nerve center are important signaling pathways for the regulation of DMV neuronal function.Then,does P in DMV also have a protective mechanism similar to the excitotoxicity of L-Glu,which changes the excitability of DMV neurons and further regulates gastrointestinal activities?In this study,the coexistence and distribution of PR and NMDAR1 in female DMV were observed by immunofluorescence double labeling technique.Different concentrations of progesterone were injected into the ovariectomized female DMV by brain stereotactic technique(control,10~1?mol/L,10~2?mol/L,10~3?mol/L,10~4?mol/L)and gradient concentrations of L-Glu(control,0.05 mol/L,0.10 mol/L,0.15 mol/L and 0.20 mol/L),The BF-420 biosignal acquisition system was used to monitor the changes of duodenal myoelectric activity and establish a mathematical model to study the synergistic mechanism of P and L-Glu in DMV.The study yielded the following main results:(1)In rabbit DMV,NMDAR1 expression was strongly positive and PR expression was moderately positive.(2)When L-Glu was injected by DMV,the duodenal myoelectric activity of rabbits was significantly enhanced(P<0.01),and the duodenal myoelectric activity index showed an"S"trend with the change of L-Glu concentration.The function expression between the two is:y=13.71/1+exp[-22.35×(x–0.082)].(3)When the progesterone was injected alone in DMV,only the 10~4 mmol/L concentration group,the amplitude of duodenal myoelectricity and the inhibition of myoelectric activity index(P<0.05),the other groups were all on the twelve fingers.Intestinal myoelectric activity was not significantly affected(P>0.05).(4)The results of synergistic effect of P and L-Glu microinjection in DMV showed that the inhibitory effect of L-Glu-induced DMV on duodenal myoelectricity in female rabbits was limited in the 10~1?mol/L concentration group(P>0.05).When the P concentration reached 10~3?mol/L,the inhibitory effect on duodenal myoelectric activity was the largest(P<0.01).When the P concentration continued to increase to 10~4?mol/L,the inhibitory effect would not continue.Increase.The inhibitory intensity of P on duodenal myoelectric activity has a significant relationship with the concentration of L-Glu.The higher the concentration of L-Glu in a certain range,the stronger the inhibition ability of P on duodenal myoelectric activity.(5)Based on each progesterone concentration group,a model between L-Glu 10~1?mol/L concentration and duodenal myoelectric activity index was established.It was found from to 10~4?mol/L by comparing the parameters of each function.The value of a gradually decreased,which means that with the increase of progesterone concentration,the duodenal myoelectric activity index can reach the theoretical maximum gradually decreasing,in addition to 10~1?mol/L,10~2?mol/L,10~3?mol/L and control.The value of a was increased compared with the group,but the value of 10~4?mol/L was smaller than that of the control group.Compared with the control group,Xc increases overall,showing the overall right shift on the coordinate axis,and Xc represents the sudden change point of the function model,that is,the function model transforms from exponential growth to logarithmic growth with increasing L-Glu concentration,overall right In the case of progesterone action,only the increase of L-Glu concentration can reach the inflection point of the mutation,and the Xc from 10~1?mol/L to 10~4?mol/L shows a gradual decline.The k-value experimental group was relatively reduced compared with the control group,and the k value from 10~1?mol/L to10~4?mol/L gradually increased,indicating that the rate of change with the increase of progesterone concentration at the mutation point is larger,by the exponential function.The change to the logarithmic function is more pronounced.The above results demonstrate that P can exert a regulatory effect on the duodenum of rabbits through the L-Glu pathway of DMV,and it has a concentration-dependent,which proves that P is directly mediated by the receptor,and the hypothalamus-pituitary-target gland In addition to the role of the two pathways in gastrointestinal regulation,there may be pathways that indirectly regulate gastrointestinal function in the nervous system.