Inhibitory Effects of Ligustrazine Plus Emodin on Expression of VEGF-related Factors in Ascites Carcinoma Walker-256 Cells / 中国实验方剂学杂志

Objective:To investigate the effects of ligustrazine combined with emodin on angiogenesis of ascites carcinoma Walker-256 cells by observing their inhibition against nuclear factor-<italic>κ</italic>B （NF-<italic>κ</italic>B）， hypoxia-inducible factor-1<italic>α</italic> （HIF-1<italic>α</italic>）， and vascular endothelial growth factor-C （VEGF-C） in HIF signaling pathway. Method:Fifty SD rats were randomly divided into sham operation group， model group， ligustrazine group， emodin group and ligustrazine combined with emodin group. Following the in situ injection of rat ascites carcinoma Walker-256 cells into the liver of normal rats， they were grouped and administered with ligustrazine （10 mg·kg^-1）， emodin （10 mg·kg^-1）， and ligustrazine （10 mg·kg^-1） plus emodin （10 mg·kg^-1） for seven days. Afterwards， the tumor-inoculated liver tissue was sampled from the experimental group and prepared into pathological sections for investigating tumor cell survival and VEGF expression. The <italic>in vitro</italic> hypoxia and hypoglycemia model （oxygen-glucose deprivation model）， hypoxia model， and hypoglycemia model of Walker-256 cells were constructed respectively. In the ligustrazine group， emodin group， and ligustrazine combined with emodin group， three consecutive concentrations that did not affect the proliferation of Walker-256 cells were selected for investigation. The drugs were administered before modeling， and the model treatment lasted for 4 h. The levels of HIF-1<italic>α</italic>， VEGF-C， and NF-<italic>κ</italic>B in the cell culture supernatant of each group were tested. Result:After the rat liver was inoculated with Walker-256 cells， the total liver mass was significantly increased（<italic>P</italic><0.05）， higher than that in the ligustrazine group， the emodin group， or the ligustrazine combined with emodin group（<italic>P</italic><0.05）. Histopathological examination showed that the response of VEGF expression in the liver tissue of each administration group was lower than that of the model group. At the cellular level， the levels of HIF-1<italic>α</italic>， VEGF-C， and NF-<italic>κ</italic>B in oxygen-glucose deprivation model of the ligustrazine group and the ligustrazine combined with emodin group were significantly reduced（<italic>P</italic><0.05）， exhibiting a certain dose-dependent response， followed by the reduction in the hypoxia model. The levels of HIF-1<italic>α</italic> and NF-<italic>κ</italic>B in the oxygen-glucose deprivation model and the hypoglycemia model of the emodin（1×10^-2，1×10^-3 mol·L^-1） group and the ligustrazine combined with emodin（1×10^-2，1×10^-3 mol·L^-1） group were significantly reduced， but there was no significant change in VEGF-C level of the hypoxia model of all the administration groups. Conclusion:Ligustrazine or emodin alone or their combination inhibits the abnormal increase in the weight of rat liver after inoculation with Walker-256 cells and the expression of VEGF in the liver tissue. Ligustrazine and emodin inhibit the protein expression of NF-<italic>κ</italic>B and HIF-1<italic>α</italic>， thereby reducing the gene and protein expression of metastasis-related target VEGF-A activated by HIF-1<italic>α</italic> transcription， restricting tumor cell neovascularization， and inhibiting the invasion and spread of ascites carcinoma cells. Among them， ligustrazine has the most significant effect against hypoxia. Glucose interferes with the effect of ligustrazine. The combination of ligustrazine with emodin is conducive to diminishing the intervention of glucose and stabilizing the inhibition against tumor cells.

Application prospect of hemoglobin-based oxygen carrier in kidney transplantation / 器官移植

High-quality donor organs is of significance for the success of organ transplantation. However, standard donors fail to meet the requirements of kidney transplantation due to the increasing quantity of patients with kidney failure. Marginal donor kidneys have been widely applied in clinical practice, which also poses challenges to the existing preservation methods of donor kidneys. Ischemia-reperfusion injury (IRI) is one of the critical factors affecting the early graft function after kidney transplantation. In addition, it exerts harmful effect upon the long-term survival of the graft. Current studies have demonstrated that hemoglobin-based oxygen carrier (HBOC) may reduce the IRI during kidney transplantation, effectively improve the preservation quality and prolong the preservation time of donor kidney. In this article, the research progress on HBOC in kidney transplantation was reviewed, aiming to provide reference for modifying the preservation method of donor kidney, improve the quality of donor kidney and enhance clinical prognosis of the recipients.

Effect of salidroside on regulating phenotypic expressionof human osteoblast-like MG-63 cells through HIF-1α signal passway / 中国药理学通报

Aim To investigate the effect of salidroside on the phenotypic expression of osteoblast and the possible molecular mechanism in hypoxia environment.Methods MTT, Annexin V/PI double staining, alkaline phosphatase(ALP) activity assay and enzyme-linked immnosorbent assay(ELISA) were performed respectively to detect the effect of salidroside on regulating phenotypic expression of MG-63 cells exposed to hypoxia.Then RT-PCR and Western blot were conducted to detect the expression levels of Osterix and Runx2 which were related to differentiation.At last, we investigated the expression levels of components of the HIF-1α pathway by RT-PCR,Western blot and ELISA, respectively.Immunofluorescence confocal microscope technology and luciferase reporter assay were performed to explore nuclear translocation and transcriptional activity of HIF-1α.Results Salidroside could markedly promote MG-63 cell proliferation, inhibit hypoxia-induced apoptosis, stimulate cell differentiation and promote expression levels of components of the HIF-1α pathway in hypoxia environment.Conclusion Salidroside could regulate phenotypic expression of MG-63 cells through HIF-1α/VEGF signaling pathway in hypoxia environment.

Correlation of HIF-1α level with hypoxia in keloid fibroblasts / 中华医学美学美容杂志

Objective To investigate the correlation of HIF-1α and hypoxia in keloids fibroblasts, and to investigate the mechanism that hypoxia promotes abnormal scarring by HIF-1α pathway. Methods Keloid fibroblasts cultured in vitro were placed in an incubator with different O2 concentrations. After 24 h, the keloid fibroblasts were collected for further study. Western blotting was performed to detect the expression of HIF-1α in the keloid fibroblasts. Results Relative amounts of HIF-1α in keloid fibroblasts cultured under O2 concentrations at 20 %, 10 %, 5 % and 1 % were 0. 007 ±0. 006, 0. 133 ±0. 006, 0. 537±0. 015 and 0. 903±0. 021, respectively. It indicated that hypoxia could increase the expression of HIF-lα in keloid fibroblasts. Conclusions Hypoxia can induce the expression of HIF-1α in fibroblasts of keloids. Moreover, there still is a positive relation between hypoxia and the expression of HIF-1α. Therefore, a close relationship exists between abnormal scarring and HIF-1α pathway by hypoxia.