1.Therapeutic Effects of Fibroblast Growth Factor-21 on Diabetic Nephropathy and the Possible Mechanism in Type 1 Diabetes Mellitus Mice
Wenya WENG ; Tingwen GE ; Yi WANG ; Lulu HE ; Tinghao LIU ; Wanning WANG ; Zongyu ZHENG ; Lechu YU ; Chi ZHANG ; Xuemian LU
Diabetes & Metabolism Journal 2020;44(4):566-580
Fibroblast growth factor 21 (FGF21) has been only reported to prevent type 1 diabetic nephropathy (DN) in the streptozotocin-induced type 1 diabetes mellitus (T1DM) mouse model. However, the FVB (Cg)-Tg (Cryaa-Tag, Ins2-CALM1) 26OVE/PneJ (OVE26) transgenic mouse is a widely recommended mouse model to recapture the most important features of T1DM nephropathy that often occurs in diabetic patients. In addition, most previous studies focused on exploring the preventive effect of FGF21 on the development of DN. However, in clinic, development of therapeutic strategy has much more realistic value compared with preventive strategy since the onset time of DN is difficult to be accurately predicted. Therefore, in the present study OVE26 mice were used to investigate the potential therapeutic effects of FGF21 on DN. Four-month-old female OVE26 mice were intraperitoneally treated with recombinant FGF21 at a dose of 100 µg/kg/day for 3 months. The diabetic and non-diabetic control mice were treated with phosphate-buffered saline at the same volume. Renal functions, pathological changes, inflammation, apoptosis, oxidative stress and fibrosis were examined in mice of all groups. The results showed that severe renal dysfunction, morphological changes, inflammation, apoptosis, and fibrosis were observed in OVE26 mice. However, all the renal abnormalities above in OVE26 mice were significantly attenuated by 3-month FGF21 treatment associated with improvement of renal adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) activity and sirtuin 1 (SIRT1) expression. Therefore, this study demonstrated that FGF21 might exert therapeutic effects on DN through AMPK-SIRT1 pathway.
2.Evaluation on Mechanical Damage of vWF Induced by Shear Stress in BPX-80 Centrifugal Blood Pump
Min ZHONG ; Wanning GE ; Liudi ZHANG ; Xu MEI
Journal of Medical Biomechanics 2021;36(4):E646-E651
Objective To evaluate the damage of von Willebrand factor (vWF) induced by shear stress in BPX-80 centrifugal blood pump, and determine whether it can be used as a reference pump for vWF damage research. Methods An in vitro hemolysis test platform was established according to the ASTM standards. The BPX-80 centrifugal blood pump was tested for 8 hours by using fresh porcine blood. The hemolysis level and vWF damage of hourly blood samples were then evaluated and compared with the static control group. ResultsThe hemolysis index of BPX-80 was stable and low during the test; vWF polymer with high molecular weight had a small amount of degradation, and showed no significant difference compared with the static control group; there was no significant change in the concentration of vWF antigen, which was basically consistent with the trend of the static control group. Conclusions BPX-80 centrifugal blood pump has good blood compatibility and can be used as the reference pump for vWF damage and hemolysis evaluation, thereby providing guidance for the design and optimization of new blood pumps.