Molecular Mechanisms Study Of Total Flavonoids Of Cynomoriumon Climacteric Syndrome Rats Models

Objective: To observe the effect of Total Flavonoids of Cynomorium(TFC) on perimenopausal syndrome and perimenopausal depression models of rat,to analysis therapeutic features of TFC on perimenopausal syndrome and reveal the molecular mechanism of TFC treatment for PMS. Method: Open back, cut the whole ovary in one side, and cut 80% in the other side to reproduce the perimenopausal syndrome rats models, and feed them medicines in 35 days continuously, then determine the moved distance and standing times of rats in open field respectively. On forced swimming test, determine the2-4min not moving time in 4 minutes, and determine the sugar intake in 24 hours. Measure and calculate the rats Index of thymus, spleen, uterine wet weight, and determine the contents of E2, LH, FSH in Perimenopause rats serum; methods Immunohistochemistry to measure the ER expression in Hypothalamus, pituitary, ovary, uterus, and the AR, BCL-2,BAX expression in Hypothalamus, pituitary.Copy perimenopausal depression rat model by opening back, cutting the whole ovary in one side and 80% in the other side, and combining with chronic stimulation.After administration for 35 days,determine the moved distance and standing times of rats in open field respectively. On forced swimming test, determine the2-4min not moving time in 4 minutes, and determine the sugar intake in 24 hours. Measure and calculate the rats Index of thymus, spleen, uterine wet weight. Determine the contents of estradiol(E2), testosterone(T),gonadotropin-releasing hormone(Gn RH), luteinizing hormone(LH), follicle stimulating hormone(FSH), interleukin-2(IL-2), bone gla protein(BGP) in Perimenopause depression rat serum;determine β- Endorphin(β-EP) content in Plasma, 5-hydroxytryptamine(5-HT), dihydroxyphenyl ethylamine(DA) content in brain homogenate. Methods Immunohistochemistry to measure the ER expression in Hypothalamus, pituitary, ovary, uterus, and the AR, BCL-2,BAX expression in Hypothalamus, pituitary. Result: Perimenopause rats are successfully reproduced, the horizontal moving distance, standing times, sugar water consumption, uterus, thymus, spleen index, serum E2 are all sufficiently decreased; forced swimming time is prolonged and serum FSH, LH level sufficiently rises; the AR changes in hypothalamus, pituitary, ER changes in hypothalamus, pituitary, ovary, uterus are sufficiently reduced; Bc1-2 changes in hypothalamus, pituitary is sufficiently decreased, and the Bax changes rise sufficiently. Total flavonoids in Cynomorium can improve the behavioral indicators of perimenopause rats, and can improve the level of uterus, thymus, spleen index and serum E2 and reduce the level of serum FSH, LH; increase the positive changes in hypothalamus, pituitary AR and the positive changes of ER in hypothalamus, pituitary, uterus, ovary; sufficiently increase the Bc1-2 changes in hypothalamus, pituitary and reduce the changes of Bax.Perimenopause rats are successfully reproduced, the horizontal moving distance, standing times, sugar water consumption, uterus, thymus, spleen index, serum E2, T, BGP, IL-2, β-EP level are all sufficiently decreased; The NE, 5-HT, DA level in Brain slurry decrease sufficiently; The calm time is prolonged in forced swimming, serum FSH, LH, Gn RH level increase obviously; AR changes in hypothalamus, pituitary and the changes of ER in hypothalamus, pituitary, ovary, thymus decrease obviously; Bc1-2 in hypothalamus, pituitary change decreases, Bax changes increase. Total flavonoids in Cynomorium can improve the behavioral indicators of Perimenopausal depression rats, can increase its ovary, thymus, and spleen index; sufficiently increase the level of serum E2, T, IL-2, β-EP, BGP; sufficiently increase the 5-HT, DA level in brain slurry of the rats, and decrease the serum Gn RH, FSH, LH level; sufficiently increase the AR changes in hypothalamus, pituitary and the ER changes in hypothalamus, pituitary, ovary, Uterus; sufficiently increase the Bc1-2 changes in hypothalamus, pituitary, and decrease the Bax changes. Conclusion: total flavonoids in Cynomorium can regulate the hypothalamus, pituitary, Gonadal axis through increasing E2 and make the related LH, FSH、Gn RH、BGP、IL-2、5-HT、DA、 ER、AR becoming normal, so that it can ease Perimenopause, depression and other symptoms. Total flavonoids in Cynomorium regulating Bc1-2 and Bax may be its molecular mechanisms.