| Under the guidance of theory of traditional Chinese medicine (TCM), TCM related factors of pelvic organ prolapse (POP) were studied from the aspects such as environmental factors, social factors, TCM diagnostic information and molecular biological indicators. Given the various types and severity of clinical syndromes, syndrome element differentiation is adopted to analyze the disease locations, disease natures and identify the correlation between different factors and the susceptibility and severity of POP. In the view of the mRNA expression level of related genes in the pathway of collagen degradation, the research was conducted from different perspectives to find out the molecular biological mechanism of POP Qi deficiency syndrome, and to analyze different Qi deficiency level and the disease locations and its different gene expression. The research could provide basis for the prevention, treatment, and prognosis of POP by TCM, reduces morbidity and the size of surgical trauma, and improve the quality of life for patients.Aim:1. To analyze the clinical features of POP by studying TCM related factors of POP patients.2. To investigate disease locations, disease nature and pathologic syndrome element of POP and the evolution of syndromes by the method of syndrome element differentiation.3. To study the molecular biological mechanism of Qi deficiency syndrome of POP by analyze collagen degradation pathway.Method:1. Analysis of TCM related factors of pelvic organ prolapse (POP) patients:321cases of patients with POP have been collected, the patients’personal information including age, height, weight, occupation, education, urban or rural residency, age of menopause, delivery times, delivery mode, pelvic surgery history, chronic cough, chronic constipation, other chronic diseases history and the duration and severity of pelvic organ prolapse were recorded. The influence of different factors on POP morbidityis was analyzed and TCM risk factors of POP were studied. 2. Study on the characteristics of TCM disease locations and natures of POP:The method of syndrome element differentiation and syndrome element score was used to analyze the severity of pathological factors and the characteristics of disease natures and locations of POP, and to study the relationship between the degrees of prolapsed and the disease locations and disease natures of POP.3. Study on characteristics of TCM syndrome evolution of POP:The method of syndrome element differentiation and syndrome element score was used to study the distribution of TCM syndromes of POP, and to explore the evolution of POP syndromes. The research would inspire the research on treatment, prevention, and control of POP.4. Research on the molecular biological mechanism of Qi deficiency syndrome of POP:The study were carried out based on the pathway of collagen degradation. Anterior vaginal wall with full thickness were taken from patients of experimental group and control group (144cases each); real-time PCR method was used to detect the difference of the mRNA expression of MMP-1, MMP-2, MMP-9, MMP-3, TIMP-1, LOX between the two groups,then to reveal whether the expression of genes in the process of collagen degradation changes when Qi deficiency rates, disease locations, and prolapse degree varied.Result:1. The analysis of POP related factors. The result of multivariate non-conditional Logistic regression analysis shows that age, education, occupation, delivery times, chronic constipation, and other chronic diseases are POP risk factors, while body mass index, chronic cough, abdominal surgery, delivery mode, urban or rural residency, menopause are not; age, occupation, education, delivery times are correlated with the prolapse degree of POP; age, occupation, and delivery times are positively correlated with the prolapse degree while education is negatively correlated.2. Features of the disease location and nature of POP.①Features of the disease location:POP is mainly related to spleen, liver, and kidney. The disease location evolves from spleen and liver in the early stage of POP to spleen and kidney in the later stage.②The disease natures of POP:There are Qi deficiency and local Qi stagnation in the early stage of POP. Qi deficiency, which is the basic pathological factors, exists throughout the process of POP. Qi collapse, blood deficiency, Yang deficiency, Yin deficiency and blood stasis will arise during the disease progresses.3. Correlation between the prolapse degree and the disease location and natures of POP. The prolapse degree is correlated to spleen, Qi deficiency, Qi stagnation, kidney, blood deficiency, and Yang deficiency. The prolapse degree is mainly correlated to the deficiency of spleen. The main features are the Qi deficiency of spleen and the deficiency and collapse of Qi.4. Syndrome elements of POP are always mixed. Mixed syndrome elements can usually be found in a POP patient while few patients show sole syndrome element like Oi deficiency of spleen or spleen Qi collapse. Most patients shows syndrome elements which evolves at least two vital organs:for example, liver stagnation and spleen deficiency, the Qi deficiency of spleen and kidney, the Qi deficiency of spleen, liver, and kidney, and deficiency of Qi,blood,Yin and Yang. There are kidney deficiency and blood stasis in the later stage.5. The molecular biological mechanism of Qi deficiency syndrome of POP based on studying collagen degradation. The result shows:All genes were detected in both the experimental group and the control group; the expression of MMP-1、MMP-2、MMP-3、MMP-9in POP group are higher than those in control group (P<0.05),while the expression of TIMP-1、LOX in the POP group are lower than those in control group (P<0.05). TIMP-1、LOX are highly negatively correlated to MMP-3、MMP-9; MMP-2is highly positively correlated to MMP-3、 MMP-9; MMP-3is highly positively correlated to MMP-9; LOX is negatively correlated to MMP-1、MMP-2、MMP-3、MMP-9while positively related to TIMP-1. MMP-1is positively correlated to MMP-2、MMP-3、MMP-9while negatively correlated to TIMP-1、LOX.The difference of gene expression of different prolapse degree and Qi deficiency ratings are statistically significant(P<0.01). The prolapse degree and Qi deficiency rating rising, the expression of MMP-1、MMP-2、MMP-3、MMP-9increase at the same time,while the expression of TIMP-1、LOX decreases. The gene of collagen degradation pathway is related to pathologic change in spleen, liver and kidney while the pathology of spleen syndrome element is related to the expression of multiple genes.Conclusion:1. POP is caused by multiple factors and the result of the dysfunction of multiple vital organs. Among the disease locations like spleen, liver, kidney and uterus and bladder, spleen, liver and kidney are the most common ones. Its syndrome elements of disease nature include Qi deficiency, Qi collapse, Qi stagnation, blood deficiency, Yang deficiency, Yin deficiency, dampness, blood stasis, essence deficiency and heat. The pathologic change in spleen exists throughout the process of POP, and Qi deficiency is its basic pathologic feature. For the first time,the research clarifies the syndrome element of spleen deficiency and liver stagnation at the early stage of POP, and the relationship between POP and liver and Qi stagnation; the research also supplements the features of the disease location and nature of POP. Therefore, the physiological, psychological and social status of women should be put into focus; the prevention of risk factors and intervention plan should be made to reduce morbidity. At the early stage, appropriate treatment for patients’condition should be made to delay the progress of the disease and improve the quality of life for patients.2. POP has long duration, and its syndrome elements are complicated, which always mixed by deficiency and sufficiency. As the disease evolves, sufficient syndrome develops into subordinate syndrome, which implies deficiency syndrome is the main syndrome of POP, and it has several concurrent disease locations and natures. POP patients with different prolapse. degree retain different pathologic and syndrome features. Their prolapse degree is closely related to the deficiency of spleen and Qi.3. The combination of MMPs, TIMP-1, and LOX may accelerate the collagen degradation in pelvic floor, which is the key cause of POP. The change in the expression of collagen degradation pathway gene is part of the molecular biological mechanism of Qi deficiency syndrome of POP. In the field of pathogenetic mechanism and clinical application of POP, it is important to explore the molecular biological mechanism of Qi deficiency syndrome of POP and analyze MMPs, TIMPs, and LOX that influence the metabolic change of collagen. |
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