自拟更年汤治疗绝经综合征的临床观察及延缓子宫衰老作用机制的研究
发布时间:2018-04-23 07:28
本文选题:自拟更年汤 + 围绝经期大鼠模型 ; 参考:《贵阳中医学院》2016年硕士论文
【摘要】:目的:通过临床检测治疗前后肾阳虚及肾阴阳俱虚型绝经综合征(MPS)患者血清雌二醇(E2)、卵泡刺激素(FSH)、黄体生成素(LH)水平,探讨自拟更年汤对性激素的影响。并在此基础上构建肾阳虚型围绝经期大鼠模型,通过观察相关药物对肾阳虚型围绝经期模型大鼠阴道脱落细胞、子宫指数、子宫的病理改变、子宫上血管内皮生长因子(VEGF)、雌激素受体(ER)、热休克蛋白70(HSP70)及它们的信使核糖核酸(mRNA)表达的影响,探讨自拟更年汤治疗MPS的相关作用机制。方法:临床研究:将70例肾阳虚型或肾阴阳两虚型绝经前后诸证患者随机分为治疗组和对照组,治疗组予以自拟更年汤,对照组予以教材方。观察两组患者治疗前后、治疗后组间的血清性激素(E2、FSH、LH)水平的变化情况。实验研究:采用阴道脱落细胞动情周期及各层细胞记量法筛选出自然老化的围绝经期雌性SD大鼠,臀部左右交替肌注氢化可的松构建肾阳虚型围绝经期大鼠模型,造模成功的模型大鼠被随机分为模型组、教材方组、更年汤组、替勃龙组;对照组选4月龄的青年大鼠及18月龄的老年大鼠。各给药组给予相应药物灌胃15d,于末次给药24小时后,取阴道脱落细胞于显微镜下观察阴道脱落细胞成熟指数(MI);处死大鼠后,剖取大鼠子宫称重换算子宫指数;HE染色观察子宫组织形态学改变;运用免疫组化、原位杂交方法检测子宫上HSP70、VEGF、ER、HSP70mRNA、VEGFmRNA、ERmRNA 的阳性表达情况。结果:临床研究:与治疗前比较,更年汤和教材方均能降低患者血清FSH、LH水平,上调E2水平(P均0.05);治疗后,更年汤组与教材方组比较,更年汤对FSH、LH的下调及对E2的上调作用均较教材方显著(P均0.05)。实验研究:①更年汤组与老年组、模型组比较,可使表层细胞百分率升高,底层细胞百分率降低,差异具有统计学意义(P0.05),更年汤组与替勃龙组、教材方组比较差异无统计学意义(P0.05)。②更年汤组、替勃龙组、教材方组与模型组比较,均能明显增加大鼠子宫指数(P均0.01),更年汤组、替勃龙组与教材方组比较增加较显著(P0.01)。③更年汤与模型组比较,能改善子宫萎缩情况(P0.01),更年汤组与替勃龙组比较效果相当(P0.05),与教材方组比较,其效果更佳(P0.05)。④更年汤组、教材方组、替勃龙组均能上调ER、ERmRNA、VEGF、VEGFmRNA阳性表达(P0.05),但教材方组的上调低于更年汤组及替勃龙组(P0.05),替勃龙组与更年汤组之间比较无显著差异(P0.05)。⑤更年汤组、替勃龙组与模型组、教材方组比较,能上调HSP70与HSP70mRNA的表达(P0.05),更年汤组与替勃龙组作用相当(P0.05)。结论:临床研究:自拟更年汤及教材方对肾阳虚型或肾阴阳两虚型围绝经期患者的血清FSH、LH、E2水平均有良性调节作用,且更年汤的作用更佳。实验研究:自拟更年汤能使阴道上皮细胞成熟度、子宫指数增加,具有雌激素样作用,且可能通过发挥其雌激素样作用上调ER、VEGF、HSP70、HSP70mRNA、VEGFmRNA、ERmRNA在子宫中的阳性表达,延缓子宫结构和功能的退行性改变,为卵巢提供充足的血供以维持其正常的生理功能,从而达到治疗MPS的目的。
[Abstract]:Objective: To investigate the effect of self drafted MPS (E2), follicular stimulating hormone (FSH) and luteinizing hormone (LH) on the effects of the self drafted geniin Decoction on sex hormones, and on this basis, the rat model of kidney yang deficiency perimenopausal period was constructed and the related drugs were observed on Kidney Yang. In virtual perimenopausal model rats, vaginal exfoliative cells, uterine index, uterine pathological changes, uterine vascular endothelial growth factor (VEGF), estrogen receptor (ER), heat shock protein 70 (HSP70) and their messenger RNA (mRNA) expression are discussed. Methods: clinical study: clinical study: 70 The patients with kidney yang deficiency or kidney yin and yang two deficiency syndrome were randomly divided into the treatment group and the control group. The treatment group was given the self-designed Decoction and the control group was given the textbook. The changes of serum sex hormones (E2, FSH, LH) between the two groups were observed before and after treatment. The experimental study: the estrous cycle of vaginal exfoliative cells and the experimental study: the estrous cycle of vaginal exfoliative cells and the experimental study The female SD rats with natural aging in perimenopausal period were screened by each layer of cell recording. The rat model of kidney yang deficiency perimenopausal period was constructed by alternately intramuscular injection of hydrocortisone on the hip, and the model rats were randomly divided into model group, textbook group, more year soup group, tiperon group, and 4 month old young rats in the control group and 18 month old old age group. Rats were given the corresponding drugs for 15d, and after the last dose of 24 hours, the vaginal exfoliative cell maturation index (MI) was observed under the microscope. After the death of the rats, the uterus index of the uterus weighed and the uterus index of the rats were calculated. The histological changes of the uterus were observed by HE staining; immunohistochemistry and in situ hybridization were used to detect the offspring. The positive expression of HSP70, VEGF, ER, HSP70mRNA, VEGFmRNA, ERmRNA in the palace. Results: clinical study: compared with before treatment, more year soup and teaching materials can reduce the serum FSH, LH, and increase E2 (P 0.05); after treatment, the more year soup group is compared with the textbook group, and the younger soup to FSH, the downregulation of LH is more than the textbook. Significant (P 0.05). Experimental study: 1. Compared with the old group, the percentage of surface cells increased and the percentage of the underlying cells decreased. The difference was statistically significant (P0.05). There was no statistical significance (P0.05). Group comparison, can significantly increase the rat uterine index (P 0.01), more than the year soup group, the more significant increase (P0.01). 3. Compared with the model group, it can improve the situation of uterine atrophy (P0.01), the comparison between the group and the test group is comparable (P0.05), and the effect is better (P0.05). (4) more years. The positive expression of ER, ERmRNA, VEGF and VEGFmRNA (P0.05) was up to up in the soup group, the teaching material group and the tren group, but the up regulation of the teaching material group was lower than that of the more year soup group and the tren group (P0.05), and there was no significant difference (P0.05) between the two groups (P0.05). The expression of A (P0.05) and the effect of the more annual soup group and the trendron group (P0.05). Conclusion: clinical study: the self-designed Decoction and teaching materials have a benign regulating effect on the serum FSH, LH, E2 level in the patients with kidney yang deficiency or kidney yin and yang two deficiency perimenopausal period, and the use of more year soup is better. The degree of maturity, the uterus index increases, has the estrogenic effect, and may increase the positive expression of ER, VEGF, HSP70, HSP70mRNA, VEGFmRNA, ERmRNA in the uterus by exerting its estrogen like action, delaying the degenerative changes of the uterus structure and function, providing sufficient blood supply for the ovary to maintain its normal physiological function, so as to achieve the treatment of MPS The purpose.
【学位授予单位】:贵阳中医学院
【学位级别】:硕士
【学位授予年份】:2016
【分类号】:R271.116
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