Explorations On The Pathogenesis Of Uterine Leiomyomas And The Therapeutic Effects Of Jiliu Neixiao Preparation

UTERINE LEIOMYOMAS, or fibroids, are the most common tumors of women in the child-bearing period, and the most common cause of hysterectomy. Regardless of their generally benign neoplastic character, with a canceration rate less than 0.2-0.3%, the majority of patients demonstrate clinically significant symptoms, including abnormal uterine bleeding, sensations of pressure in the pelvis, pain, and reproductive disability, etc. Their prevalence has severely affected women's healthy conditions. Therefore, it is the priority for us to enforce the research on the mechanisms of pathogenesis and treatment of uterine leiomyomas.Traditional Chinese medicine (TCM) has been considered to possess remarkably therapeutic effects, little side effects, and less recurrence rate. Based on the clinical researches of Professor Chengzong Xiao, we explored to uncover the precise pathophysiological mechanisms of uterine leiomyomas by elucidating the estrogen receptor (ER), progesterone receptor (PR), expressions of the related protein in uterine leiomyoma tissue in human. The author has attempted to establish uterine leiomyomas models in rats by loading estrogen and progesterone, with the goal of achieving a better understanding of the cellular and molecular alterations during uterine smooth muscle fibrosis, and a better understanding of the mechanisms of the pathogenesis. Under the help of the stable animal models and related techniques, we observed the therapeutic effects of Jiliu Neixiao preparation (JLNX) and its pharmacological mechanisms on experimental uterine leiomyomas in rats, under the hope of revealing a better interpretation of TCM's effects on the disease.Researches on the estrogen receptor, progesterone receptor, expression of related protein in uterine leiomyomas tissue in human.Expressions of ER, PR, proliferating cell nuclear antigen (PCNA), bcl-2, epidermal growth factor receptor (EGFR), and ERmRNA in uterine leiomyoma tissue in human were examined by immunohistochemistry, in situ hybridization, and multifunctional imagine analysis, respectively. The results indicated that the expression of ERmRNA and its transcription product (ER protein) were up-regulated distinctively in leiomyoma tissue compared with adjacent normal tissue. That indicated a hyper-estrogen status in the local tissue of leiomyoma. In addition, both expression of PR and density of positive cells are significantly higher in diseased tissue than those of normal tissue. The hyper-progesterone status played another important role in improving the process of fibrosis.Another result indicated that less PCNA-positive cells scattered in normal uterine tissue, however, more clustered positive cells were observed in abnormal tissue. The proliferative index was increasedabsolutely, which pictured the leiomyoma tissue in an excessively proliferative condition. As for the expression of bcl-2 protein, one of apoptosis-inhibiting oncogenes, the area density, mean optical density, and integrative optical density were more increased in leiomyoma tissue than those of the normal. It was safe for us to say that, by inhibiting or deferring the death of apoptotic cell, over expression of bcl-2 took an active part in the development of uterine leiomyomas. Supported by these two results, we could draw the conclusion that not only the over proliferation but also the inhibition of programed cell death enhanced the development of uterine leiomyomas.Over expressions of EGFR were also observed in leiomyoma tissue rater than in the normal tissue. Under light microscope, brown granules were scattered within the plasma of positive staining cells, which were in larger number than that in normal cells. The area density, mean optical density, and integrative optical density were much more elevated. In this regard EGFR and its receptor may act to stimulate proliferation and differentiation in fibroids through the autocrine and paracrine in local tissue.Experimental study on uterine leiomyoma rats loaded by estrogen and progesterone and the ther...