Efficacy Of Guizhi Fuling Pill Modified In Treating Uterine Leiomyoma And Its Effect On Serum MicroRNA Expression Profiles

ObjectiveThe purpose of this study was to compare the therapeutic effect of Modified Guizhi Poria Pill to treat patients with growing uterine fibroids of cold coagulation and blood stasis type based on the size of fibroids. Then, explore the possible molecular mechanism according to the differential expression of miRNAs in serum.Methods1. Patients from Augest 2014 to December 2015 in China academy of traditional Chinese medicine Guang’anmen Hospital gynecological clinics who were fit for diagnostic standard were included in this study. Group the patients according to the diameter of the biggest fibroid (small fibroid group<2.5cm; 2.5<medium-sized fibroid group<5cm; large-sized fibroid group>5cm) and compare the effect of the three groups.Treat for 3 months on the basis of Modified Guizhi Poria Pill. Observation indexes included: monthly growth volume of the fibroids, associated symptoms and safety indexs (ALT and AST).2. Select five patients randomly from the patients the volume of fibroid of which have reduced>25% after treatment as treatment group; take five healthy women as control group. Select their blood samples,isolate the monocytes and extract the total RNA. Use gene chips to detect the differential expression of miRNAs in serum,then analyse the miRNAs of differential expression using bioinformatic technologies.3. For all statistical analyses, the statistical software SPSS 21.0 was used.Mean±tandard deviation for the measurement datas with normal distribution; median for the measurement datas which are not consistent with normal distribution; the count datas are expressed in the proportion (%).Paired T test and Wilcoxon rank sum test were used for the measurement datas; Chi square was used for the count datas.Results1. After treatment, the monthly growth volumes of the fibroids of small fibroid group and medium-sized fibroid group are negative, and medium-sized fibroid group is more significant (P<0.01); the monthly growth volume of the fibroids of large-sized fibroid group is reduced (P>0.05).2. After treatment, the proportions of menorrhagia,small abdominal pain, clots,remenstrual breast swelling and soreness are significantly reduced(P<0.01).3. After treatment, the proportions of symptoms including impatient irritability, moodiness and thirst, frequent urination, painful intercourse are reduced (P<0.05).4. The ALT and AST levels were in normal range before and after the treatment, which show no significant change (P> 0.05).5. Before treatment,there are 96 miRNAs in serum expressed differentially between treatment group and control group,55 miRNAs up-regulated,41 miRNAs down-regulated. After treatment,1 miRNAs up-regulated and 18 miRNAs down-regulated of the 96 miRNAs. Among the 19 differential expressed miRNAs, only 17 miRNAs down-regulated have target genes.6. After pathway analysis of target gene prediction and functional enrichment of the 17 miRNAs down-regulated, four KEGG pathways related with uterine fibroids.are obtained, namely:MAPK signaling pathway, Wnt signaling pathway, mTOR signaling pathway, PI3K-Akt signaling pathway.Conclusions1. Modified Guizhi Poria Pill could block the growth of uterine fibroids and even shrink small-sized and medium-sized fibroids and slow down the speed of the growth of larged-sized fibroids.2. Modified Guizhi Poria Pill could improve menstruation.3. Modified Guizhi Poria Pill could improve related symptoms.4. The possible molecular mechanism of Modified Guizhi Poria Pill may through the regulation of specific miRNAs to inhibite related KEGG pathways to block the growth of fibroids and even shrink fibroids.