| Objectives:1. To observe the clinical efficacy of Busui Shengxue Granule in chronic aplastic anemia (CAA) patients.2. To explore the roles of FAK/PI3K signaling transduction pathway and Rho GTPase in CAA pathogenesis of abnormal hematopoietic adhesion. We observed the influences on FAK/PI3K signaling transduction pathway and Rho GTPase in CAA patients with Busui Shengxue Granule.Methods:1. One hundred and eight patients of CAA were divided into two groups at random, the experimental group contained 55 cases, and the control group contained 53 cases. The experimental group was treated by Busui Shengxue Granule, while the control group was treated by Zaizao Shengxue Tablet. All the patients should be treated for 6 months at least.2. After 6 months of treatment, compared the differences of clinical efficacy, traditional Chinese medicine (TCM) symptoms, the efficacy of TCM syndromes, peripheral blood and bone marrow in the two groups.3. Before and after treatment, the protein expression of some enzymes and theirs phosphorylation levels in FAK/PI3K signaling transduction pathway of CAA patients were examined by Western blot, the protein expression levels of Rho GTPase ware examined by Western blot too, and the mRNA expression levels of FAK and PI3K p85 in bone marrow mononuclear cells of CAA patients were examined by RT-PCR.Results:1. The total clinical effective rate of Busui Shengxue Granule in CAA patients was 74.55%, significantly better than the control group (P<0.05). Busui Shengxue Granule could significantly regulate the frequencies and average score of TCM clinical symptoms significantly (P all<0.05), the total effective rate of TCM syndromes in experimental group was 87.27%, significantly higher than the control group (P<0.05).. While improving WBC, Hb and PLT in CAA patients'peripheral blood, the experimental group was better than control group (P all<0.05). The clinical efficacy of CAA patients in Kidney-Yang deficiency type was superior to Kidney-Yin (P<0.05).2. The protein expression levels of FAK, phospho-FAK Tyr397 and mRNA expression levels of FAK in CAA patients'bone marrow mononuclear cells were lower than the normal control group (P all<0.05), Busui Shengxue Granule could increase the abnormal expression levels of these three (P all<0.05), and the significant difference existed in the experimental group and control group (P<0.05). While regulating the expression levels of FAK and FAK mRNA, the Kidney-Yang deficiency type was better than Kidney-Yin (P all<0.05), and the mRNA expression levels of FAK could be up to the normal control group (P>0.05).3. The protein expression levels of PI3K, phospho-PI3K p85 and the mRNA expression levels of PI3K p85 in CAA patients'bone marrow mononuclear cells were significantly lower than the normal control group (P all<0.05), Busui Shengxue Granule could improve the expression levels all of them (P all<0.05). In improving the protein expression levels of PI3K and phospho-PI3K p85, the experimental group was better than control group (P all<0.05). Before treatment, the protein expression levels of PI3K in Kidney-Yang deficiency type were higher than Kidney-Yin (P<0.05). After treatment, the significant difference existed in regulating PI3K p85 mRNA between the two types (P<0.05).4. The protein expression levels of RhoA, CDC42 and Rac in CAA patients'bone marrow mononuclear cells were lower than the normal control group (P all<0.05), Busui Shengxue Granule could increase the levels all of them (P all<0.05). In improving the protein expression levels of RhoA and CDC42, the experimental group was better than control group (P all<0.05). Before treatment, the protein expression levels of CDC42 in Kidney-Yang deficiency type were higher than Kidney-Yin (P<0.05). After treatment, the significant difference existed in regulating RhoA and CDC42 between the two types (P all<0.05).Conclusion:1. The clinical efficacy of Busui Shengxue Granule in CAA patients was significant, it reminded us that treating CAA should be invigorating kidney based on kidney. 2. The low expression of FAK in bone marrow mononuclear cells might have a certain relationship with CAA pathogenesis of abnormal hematopoietic adhesion.3. The low expression of PI3K and PI3K p85 in bone marrow mononuclear cells might be involved the pathogenesis of CAA.4. The abnormity of FAK/PI3K signal transduction pathway integrin-mediated might be a key link in CAA pathogenesis of abnormal hematopoietic adhesion.5. The low expression of Rho GTPase, including Rho, CDC42 and Rac, might affect the mechanisms of hematopoietic stem cell homing and migration.6. Busui Shengxue Granule could improve some enzymes in FAK/PI3K signal transduction pathway and Rho GTPase family, make FAK/PI3K signal transduction pathway and Rho GTPase family to activate, the mechanisms might improve the formation of focal adhesions, regulate cytoskeleton, promote hematopoietic cell proliferation, differentiation, improve the hematopoietic microenvironment, so as to improve the hematopoietic stem cell/progenitor cell homing, migration, and enhance the adhesion of hematopoietic signal transduction, then the hematopoietic function to resume.7. The clinical efficacy of Busui Shengxue Granule in Kidney-Yang deficiency type is higher than Kidney-Yin in CAA patients. Meanwhile, in Kidney-Yang deficiency type, the protein expression levels of FAK, RhoA, CDC42 and mRNA expression levels of FAK, PI3K p85 also could be better corrected than in Kidney-Yin.
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