Study Of The Pathomechanism And TCM Syndrome Differentiation Of Ovarian Hypofunction In Rat Model Caused By Tripterygium Glycosides

OBJECTIVE:In order to have better animal models with required TCM syndrome characters for pharmacodynamic research in the effects of TCM treatment on female reproductive system, based on TCM theories and our previous research in making mouse models, Tripterygium Glycosides is given to rats to make a repeatable and reliable model of ovarian hypofunction. Method of "syndrome identification with medicine" is applied to study the TCM syndrome characters of the model and the action mechanism of intervention treatment for the model.METHODS:selected SD rats in child-bearing period checked with colpocytogram had normal estrous cycles and were included for study. Six of them were randomly selected as normal controls, and the others were all given intragastric administration with tripterygium glycosides 40mg/kg/day over 10 weeks to make the required models by using methods of our previous research. The models were successfully made when their monitored estrous cycles all became disordered.30 of the modeled rats were selected and randomly divided into five groups. Each group had six rats. Premarin and three different dosages (high, medium and low) of herbal compound "Tong Mai Da Sheng Pian" were given to four of the five groups respectively for 7 days, while one group set as normal model control was given similar volum of normal sodium for 7 days. Their general condition and representation were all noted. Their ovarian indexes were measured by tissue-weight-assay when sacrificed at the end of the treatment. Their serum "E2" and "P" were tested with LEIA, Inhibin B with ELISA, and "ER", " PR", "TNF-α/TNFR-1", " Caspase-3", "VEGF/Flk-1", and "Endostatin" with EIHCT. Pathological examinations were performed on their ovarian slides with HE stain to observe the histomorphological changes of ovarian cells with optical microscope.RESULTS:(1) Intragastric administration with tripterygium glycosides 40mg/kg/day over 10 weeks for a rat in child-bearing period can change it into a status of ovarian hypofunction which manifestations of bad general conditions and disordered estrous cycles, and significant decreases in their ovarian indexes, serum levels of E2, INHB growing follicale number, ER expression in ovarian tissue and VEGF expression in ovarian vessel, but obvious increase in the expressions of Endostatin, TNF-a and Caspase-3. The number of growing follicle in ovarian tissue decrease, and vessel wall thickening, lumen of blood vessel narrowing(2) After the interventional treatment with "Tong Mai Da Sheng Pian", the modeled rats can have obvious improvement in their general conditions with normal estrous cycles and enhanced ovarian indexes, and significant increases in E2, INHB, but obvious decreases in Endostatin, TNF-a and Caspase-3. The number of growing follicle in ovarian tissue increase, and vessel wall thinningz, lumen of blood vessel broaden.CONCLUSION:(1) The tripterygium glycosides can cause ovarian hypofunction in rats, while herbal compound "Tong Mai Da Sheng Pian" with functions to tonify Kidney Qi and nourish Blood and Essence can increase estrogen and ER levels, ovarian hemoperfusion, and inhibit ovarian apoptosis, and improve ovarian function effectively. (2) The effectiveness of treatment with the herbal compound tonifying Kidney verifies the rat model with TCM syndrome of Kidney Deficiency in Qi and Essence.