Hypoxia-inducible factor-1α attenuates renal podocyte injury in male rats in a simulated high-altitude environment by upregulating Krüppel-like factor 4 expression.

Previous studies have shown that podocyte injury is involved in the development of proteinuria in rats under hypobaric hypoxia conditions. Prolyl hydroxylase inhibitors (PHIs) may reduce proteinuria. This study aimed to further investigate whether the protective effects of hypoxia-inducible factor 1α (HIF1α) on podocyte injury induced by hypobaric hypoxia are related to Krüppel-like factor 4 (KLF4). Rats were housed in a low-pressure oxygen chamber to simulate a high-altitude environment (5000 m), and a PHI was intraperitoneally injected. Urinary protein electrophoresis was performed and the morphology of the podocytes was observed by electron microscopy. Rat podocytes were cultured under 1% O2, and siRNA was used to interfere with KLF4 expression. The protein expression levels of HIF1α, KLF4, CD2-associated protein (CD2AP) and nephrin were determined by western blotting. Compared with those in the experimental group, the rats in the intervention group on day 14 had lower urinary protein levels, increased protein expression levels of CD2AP and nephrin, and reduced podocyte injury. The results of in vitro experiments showed that the protein expression levels of KLF4, CD2AP and nephrin were greater in the PHI intervention group and lower in the HIF1α inhibitors group than in the low-oxygen group. The protein expression of CD2AP and nephrin in the siKLF4-transfected podocytes treated with PHI and HIF1α inhibitors did not differ significantly from that in the low-oxygen group. HIF1α may be involved in reducing progressive high-altitude proteinuria by regulating KLF4 expression and contributing to the repair of podocyte injury induced by hypobaric hypoxia.

Establishing a hemodialysis vascular access with autologous vein transplantation / 中国组织工程研究

BACKGROUND:Currently, literatures about autologous vein transplantation are few, and the research on the effect of different parts of autologous vein transplantation are not found yet. OBJECTIVE:To summarize the experiences of establishing the fistula using autologous vein transplantation so as to investigate the method of improving the success rate of surgery. METHODS:We analyzed retrospectively the data of 40 cases of establishing the fistula using autologous vein transplantation, and then compared the successful rate of autologous vein transplantation fistula, blood flow and operating time, thereby analyzing the influence of diabetes melitus on the successful rate of autologous vein transplantation fistula. RESULTS AND CONCLUSION:The successful rates of autologous vein transplantation fistula at different parts ranging from high to low were as folows: the cephalic vein, great saphenous vein, basilic vein and smal saphenous vein. Blood flow of the upper limb for vein transplantation fistula was obviously higher than that of the lower limb (P < 0.05). The operating time of autologous vein transplantation fistula was longer in the upper limbs than in the lower limbs (P < 0.01). For patients with diabetes melitus, the successful rate of autologous vein transplantation was markedly lower than those with no diabetes melitus (P < 0.01). For the hemodialysis patients with poor upper limb superficial vein, autologous vein transplantation is a better way of establishing the vascular access. Vein transplantation of the upper limbs is better than that of the lower limbs in success rate and operating time. Autologous vein transplantation fistula is not suitable for the patients with diabetes melitus.

Regulation of transcriptional factor NF-E2-related factor 2 by different doses of TNF-α / 中国病理生理杂志

AIM: To study the effects of tumor necrosis factor-α (TNF-α) on the transcriptional activity of nuclear factor-erythroid 2-related factor 2 (Nrf2) in pulmonary microvascular endothelial cells. METHODS: Rat pulmonary micro-vascular endothelial cells (PMVECs) were cultured by lung tissue block pasted methods, and identified immunocytochemically using Ⅷ factor-related antigen. The cells were treated with different doses TNF-α (prepared in serum-free medium) for 4 h. Subcellular localization and levels of Nrf2 in PMVECs were observed with immunocytochemical methods. Nuclear extract were obtained to assayed transcriptional activity of Nrf2 with EMSA. Total RNA were isolated to assay the mRNA expression of Nrf2 by RT-PCR. RESULTS: The protein level of Nrf2 in the nuclei and transcriptional activity increased dose-dependently in PMVECs after treated with TNF-α at concentrations of 2.5, 5.0 or 10.0 μg/L. However, the protein level of Nrf2 in nuclei and transcriptional activity decreased dose-dependently in PMVECs after treated with TNF-α at concentrations of 20 or 40 μg/L. No different mRNA expression of Nrf2 in PMVECs treated with TNF-α at all concentration above was observed. CONCLUSION: Transcriptional activity of Nrf2 increases in PMVECs treated with low or moderate doses of TNF-α and decreases in PMVECs treated with high doses of TNF-α.