Observation Of Curative Effect Of BSHXT On MVA Among Post-menopause Women And The Mechanism Of Action

BackgroundEpidemiology study has shown that the incidence of CD among postmenopausalwomen has risen obviously and it accounts30%of the death of postmenopausal women.The risk for myocardial infarction, congestive heart failure and sudden death duringpost-menopause is twice higher than pre-menopause. Among the cardiovascular diseasesin postmenopausal women, coronary microvascular disease has drawn wide attention fromcardiovascular scholars both at home and abroad for its substantial morbidity, repeatedoutbreak and heartstroke. Coronary microvascular disease can severely affect the quality oflife and work. Besides, CD can be developed because of poor prognosis.MVA is a common coronary microvascular disease that can not be cured completelyby Western medicine treatment which can only reduce the myocardial oxygenconsumption and alleviate the symptoms. Consequently, the functional repair ofendothelial cells becomes the focus to cure MVA. The high incidence of MVA amongpost-menopause women indicates that it has a lot to do with estrogen. A variety of studiessuggest that EST have a protective effect for vascular endothelial cells, but its application islimited by the potentially risen risk of breast cancer and breast cancer. Therefore, thesearch for drugs to repair endothelial cell damage is still the focus in cardiovascular field.Currently, Chinese traditional treatment of MVA is mainly based on blood stasis butseldom on kidney deficiency. TCM（traditional Chinese medicine） holds that heart is theyang aspect of yang and kidney is the root of arch-yin and arch-yang. After menopause, women are more likely to suffer from MVA, when deficiency of kidney, the kidney yinand the insufficiency of kidney yang occur. For that reason, we consider that the mainlocation of MVA is in the heart and root is kidney. In addition, MVA is closely related toaffect-mind dissatisfaction. So invigorating the kidney and promoting blood circulation isthe key therapeutic method to cure MVA. BSHXT (formerly flavored EXT) is developedwith EXT（which is helpful for tonifying kidney and replenishing essence） as well aspuerarin, Polygala amflra and processed cyperus（which are conductive to promotecirculation of qi and relieve uneasiness of mind and body tranquilization）.Our preliminary study shows that BSHXT can not only cure MVA of post-menopausewomen, but also prevent and cure hypertension of elderly women, and it can inhibit theNF-κBp50–IκBα pathway. This is an important mechanism of the BSHXT Decoctionmyocardial protection; at the same time this part can increase the expression of aortic ERβin ovariectomized rats, which may be related to the increase of E2in blood plasma. Toknow the mechanism of action of BSHXT further，we research the effect of it to theestrogen/the number of cardiac microvessel and to the structure and function of cardiacmicrovessel and endotheliocyte, which can not only to offer effectual medicine to treatMVA, but also to supply experiment groundwork to the further research and developmentof BSHXT.Part one Observation of curative effect of BSHXT on MVA among post-menopausewomenObjective: To confirm the curative effect of BSHXT which is helpful for reinforcing kidney,replenishing essence, promoting blood circulation and relieving uneasiness of mind andbody tranquilization for post-menopause microvascular angina by clinical observation.Methods: Subjects who meet the inclusion criteria of clinical trial（80were enrolled andrandomly divided into the treatment group and the control group. A randomized,single-blinded, parallel-controlled trial is then conducted among the control group. Thegeneral condition and clinical symptoms were observed. Detection indexes such as blood,urine and stool routine, liver and kidney function，the frequency of stenocardia， as wellas treadmill exercise test were set.Results: The incidence rate of angina among treatment group was significantly lower thancontrol group. After treatment, the movement duration of treatment group was significantly longer than that of control group. It took much longer for treatment group tomove to1millimeter below ST-segment. Treatment group showed better improvement inST-segment than control group. After treatment, there were no significant abnormalities inblood, urine and stool routine, as well as liver and kidney function in both of the twogroups.Conclusion: Through clinical observation it can be concluded that compound BSHXT issafety and highly effective for post-menopause microvascular angina, while it doesn’tinfluence liver and kidney function. This result will provide foundation for clinical studyof compound kidney-supplementing blood-quickening decoction.Part-two Effect of BSHXT on cardiac function, structure and function of cardiacmicrovessel and endotheliocyte in ovariectomized ratsObjective: To observe the Effect of BSHXT on the general condition, cardiac function andthe morphology and function of microvessel and endothelial cells of ovariectomized rats.Methods: Random allocation was taken to divide forty-eight3-month-old adult femalerats into eight groups: normal group, sham operation group, ovariectomized group(themodel group), ovariectomized+higher dose of BSHXT (the higher-dose group of Chinesemedicine), ovariectomized group+lower dose of BSHXT (the lower-dose group ofChinese medicine), ovariectomized+17β estradiol intervening group(positive controlgroup), ovariectomized+higher dose of BSHXT+estrogen receptor inhibitor, andovariectomized+lower dose of BSHXT+estrogen receptor inhibitor(ICI182780group).The general condition of experimental rats before and after taking BSHXT was observed.The changes of weight were measured regularly. The cardiac function of experimental ratswas detected by B-ultrasonic while their microvessel was labeled by immunofluorescence.Furthermore, the structure of microvessel and the change of its quantity were observedthrough a microscope. Besides, the organelle changes of microvascular endothelial cellswere observed through transmission electron microscopy. In addition, the content of E2、ET、PGI2、TXA2of rats were measured by radioimmunoassay, the content of NO wasmeasured by enzymatic determination.Results:1. Compared with the blank control group and the sham operation group, rats ofovariectomized group became overweight to different degrees, and their fur became yellow and began to loss.2. E2in blood plasma of experimental rats in the model group decreased obviouslycompared with that in the normal group, while it increased significantly in the TCM groupcompared with that in the model group, but there was no obvious change compared in theEstrogen group. ET-1in the TCM group was decreased especially for the higher dosegroup compared with that in the model group. N0in the TCM group slightly increased butnot obvious compared with that in the control group. TXA2in the TCM group decreasedsignificantly especially for the higher dose group, while PGI2increased significantlycompared with that in the control group.3. The myocardial injury and the damage of organelle structure of microvascularendothelial cells in the model group and the oestrogen intervening group were moreserious than those in the normal group, while it was improved for the TCM group and theoestrogen intervening group. There was relationship between efficacy and doses.4. According to cardiac ultrasound results, the indexes of the observed group weresignificantly improved compared with that in the model group, especially for the higherdose group and the oestrogen intervening group. While LVFE increased significantlycompared with that in the control group.Conclusion: BSHXT can reduce the weight of ovariectomized and prevent themorphological and functional damage of microvessel and endothelial cells ofovariectomized rats. Consequently, cardiac insufficiency of ovariectomized rats can beprevented which may be related to the increase of E2in blood plasma,so BSHXT maytoproduce a marked effect as the phytoestrogen.