1.Relationship between the gene polymorphisms of transforming growth factor beta 1 and interleukin 1 beta and primary knee osteoarthritis in Xinjiang Han and Uygur populations
Haitao LI ; Fuyu CHEN ; Weishan WANG ; Defeng MENG ; Jiang PENG ; Shibi LU ; Chenhui SHI
Chinese Journal of Tissue Engineering Research 2017;21(24):3906-3911
BACKGROUND:Transforming growth factor β1 (TGF-β1) and interleukin 1β (IL-1β) have been reported to play an important role in the occurrence and development of primary osteoarthritis. OBJECTIVE:To investigate the association between gene polymorphisms of TGF-β1 and IL-1β and primary knee osteoarthritis. METHODS: Han and Uyghur elderly populations in Xinjiang Uygur Autonomous Region, China were surveyed on the prevalence of osteoarthritis, followed by allotted to osteoarthritis and health groups according the symptoms and radiography. Genotyping TGF-β1-509C/T and -1348C/T and IL-1β-511C/T was performed to analyze the relationship between the gene polymorphisms of TGF-β1 and IL-1β and osteoarthritis. RESULTS AND CONCLUSION:Alleles T and C with genotypes CC, CT and TT were detected in both two groups. In the Uygur population, the genotype frequency of TGF-β1-509C/T and IL-1β-511C/T showed significant difference between osteoarthritis and health groups (P < 0.05). In the Han population, the genotype frequency of TGF-β1-1348C/T showed significant difference between two groups (P < 0.05). These results suggest that the Uygur individuals carrying TT genotype of TGF-β1-509C/T and IL-1β-511C/T, and Han people carrying the TT genotype of TGF-β -1348T are more susceptible to osteoarthritis.
2.Effect of Gualou Xiebai Banxiatang on Myocardial Microangiogenesis and HIF-1α/VEGF-related Pathways in Myocardial Ischemia Model Rats
Wenhao CHEN ; Weishan MENG ; Hong LI ; Weiwei TIAN ; Qi ZHANG ; Yingying TAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):1-9
ObjectiveTo investigate the effect of Gualou Xiebai Banxiatang on cardiac function and myocardial histopathological changes in rats with ischemic myocardial injury, and to observe the effect of myocardial microvascular density (MVD), phosphatidylinositol 3-kinase (PI3K), mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) signaling pathways on myocardial microangiogenesis. MethodSeventy male SD rats were randomly selected, with six rats in the normal group. The remaining rats were fed a high-fat diet and injected with isoproterenol hydrochloride (ISO,80 mg·kg-1·d-1, 2 d) to induce a hyperlipidemia-based ischemic heart disease model. After successful modeling, the rats were randomly divided into the model group, high, medium, and low dose groups of Gualou Xiebai Banxiatang, and the metoprolol group. The high, medium, and low dose groups of Gualou Xiebai Banxiatang were given Gualou Xiebai Banxiatang at 10.42, 5.21, 2.61 g·kg-1·d-1, respectively, while the metoprolol group was given metoprolol at 2.6 mg·kg-1·d-1. Both the normal and model groups were given an equivalent volume of physiological saline for 28 days. After the intervention, relevant tests were conducted, and serum was collected to measure heart function-related indicators. Hematoxylin-eosin (HE) and Masson staining were performed on ventricular tissue to observe pathological changes under a light microscope. Immunohistochemistry (IHC) was used to detect the positive expression of platelet endothelial cell adhesion molecule (CD31). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of N-terminal pro-brain natriuretic peptide (NT-proBNP) and VEGF. Western blot was used to detect the protein expression levels of PI3K/mTOR/HIF-1α/VEGF. ResultCompared with the normal group, the model group showed significantly increased serum levels of LDH, CK, CK-MB, NT-proBNP, and VEGF (P<0.01), significantly increased collagen volume fraction (CVF) (P<0.01), significantly decreased MVD (P<0.01), and elevated protein expression levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.05, P<0.01). Compared with the model group, the metoprolol group had significantly lower serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.01), significantly higher VEGF levels (P<0.01), significantly decreased CVF (P<0.01), significantly increased MVD (P<0.01), and significantly increased protein expression levels of PI3K, mTOR, and VEGF (P<0.01), with no statistically significant change in HIF-1α protein expression. Compared with the model group, the high and medium dose groups of Gualou Xiebai Banxiatang had decreased serum levels of LDH, CK, CK-MB, and NT-proBNP (P<0.05, P<0.01), increased VEGF levels (P<0.05, P<0.01), significantly reduced CVF (P<0.01), increased MVD (P<0.05, P<0.01), and significantly increased protein levels of PI3K, mTOR, HIF-1α, and VEGF (P<0.01). In the low dose group of Gualou Xiebai Banxiatang, compared with the model group, serum levels of LDH and NT-proBNP were decreased (P<0.05), VEGF was increased (P<0.05). Moreover, CVF was decreased (P<0.05), and the protein expression levels of PI3K, mTOR, HIF-1α, and VEGF were significantly increased (P<0.01). ConclusionGualou Xiebai Banxiatang can improve cardiac function, reduce myocardial pathological damage, enhance endothelial cell function, promote myocardial microvascular formation, and upregulate the expression of PI3K, mTOR, HIF-1α, and VEGF proteins in myocardial tissue in rats with ischemic myocardial injury.