The Clinical Effect Of Shugan Jianpi Method On HPRL And The Mechanism Of Hypothalamic Dopamine D2 Receptor Calcium Ion Pathway

The purpose of this paper was to observe the clinical curative effect of Xiaoyao san formula in treating Hyperprolactinemia(HPRL)and to observe the tinfluence of calcium channel signal transduction mechanism of dopamine D2 receptor on HPRL model rat,which makes the calcium channel signal transduction mechanism of dopamine D2 receptor as a target to investigate the etiology and pathogenesis of HPRL and as one function chennel of intervention of Traditional Chinese Medicine(TCM)?Meanwhile,it can provide clear and reasonable treatment and modern theory basis for TCM in the treatment of HPRL.The research have two parts:clinical research and experimental research.We divided 60 patients,who's collected from Chinese medicine hospital of Guizhou province with HPRL,into treatment group and control group randomly.Treatment group with Xiaoyao san formula,the control group with bromocriptine.After taking three menstrual cycles,we observed the improvement clinical symptoms,the change of PRL level,the recurrence rate and incidence of adverse reactions of the patients with HPRL treating by Xiaoyao san formula.Experimental research:We choose SD female rats,weight of 200 g± 20 g,the method of making HPRL model rats is to do pituitary(which is provede from donor rat)transplantation in renal capsule of receptor.We divided 56 SD sexual maturity female rats randomly into normal blank group(no modeling),negative control group(model group),Chinese medicine middle dose group,Bromocriptine group,D1 receptor antagonist group,D1 receptor antagonist +Chinese traditional medicine group,D1 receptor antagonist +Bromocriptine group.After modeling,normal blank group with normal feed for.30 days:negative control group with normal saline intragastric administration for 30 days:Chinese medicine middle dose group with Xiaoyao san formula(According to 10 times of clinical dosage calculation)intragastric administration for 30 days,once per day:Bromocriptine group with bromocriptine intragastric administration for 30 days,once per day:D1 receptor antagonist group with D1 receptor antagonist SCH23390(lmg/kg)intraperitoneal injection for 30 days,once per day:D1 receptor antagonist+Chinese traditional medicine group with D1 receptor antagonist SCH23390(lmg/kg)intraperitoneal injection 30 minutes before and Xiaoyao san formula(According to 10 times of clinical dosage calculation)intragastric administration for 30 days,once per day:D1 receptor antagonist +Bromocriptine group with Dl receptor antagonist SCH23390(lmg/kg)intraperitoneal injection 30 minutes before and bromocriptine intragastric administration for 30 days,once per day.After 30 days,we take the blood and the hypothalamus by decollation,test PRL level and IP3 on the hypothalamus of each group by using Ruzymelinked Immunosorbent Assay,and test the change of PKC and CaMK on the hypothalamus of each group by using Western blot.Results:1.clinical research:Xiaoyao san formula and bromocriptine both can reduce the PRL level of patients with HPRL.Symptoms improvement,the incidence of adverse reactions and the recurrence rate is better than the control group(P<0.05).2.Experimental research:(1)Xiaoyao san formula can reduce PRL level of rats serum,there were statistical significance by compared with model group(P<0.05).(2)Compared with model group,in addition to the SCH23390 group,the IP3 concentration of other groups were increased significantly(P<0.01),which could make the further signal transduction of calcium channel,and produce the effect of PRL secretion decline eventually.(3)Compared with model group,the PKC,CaMK grey value of other groups were increased significantly besides the SCH23390 group(P<0.01),which can open calcium channel to reducing Ca2+ concentration of intracellular by Ca2+ flowing of the endoplasmic reticulum,then,lower the levels of protein phosphorylation in cells so as to the decline of PRL secretion.Conclusion:1.Xiaoyao san formula have curative effect in the treatment of HPRL patients which is well-matched to bromocriptine.The improvement of the symptoms,adverse reactio and recurrence of Xiaoyao san formula are better than bromocriptine.2.the experimental study shows that Xiaoyao san formula can significantly reduce the serum PRL level of model rats.The mechanism is by increasingexpression of IP3,PKC and CaMK in rats' hypothalamus of rats,thereby better open Ca2+ channels,to further strengthen the dopamine D2 receptor signal transduction,have a corresponding effect of reducing PRL secretion.