基于RAS/RAF/ERK信号通路探讨益气生肌合剂对压力性损伤大鼠创面微小血管生成的作用机制

目的:观察益气生肌合剂通过调控RAS/RAF/ERK信号通路对压力性损伤大鼠模型创面修复及微小血管生成的影响.方法:32只大鼠分为模型对照组、三乙醇胺乳膏组(阳性药物组)、益气生肌合剂组(益气生肌组)、三乙醇胺乳膏+益气生肌组(联合用药组),每组8只.建立压力性损伤大鼠模型并予不同方式干预.记录各组大鼠创面愈合及病理损...     

过表达血管生成抑制蛋白1对人结直肠癌细胞恶性生物学行为的影响

目的： 探讨过表达血管生成抑制蛋白1（vasohibin-1,VASH1）对人结直肠癌细胞恶性生物学行为的影响。方法： 包装慢病毒并感染人结直肠癌SW680、SW620细胞以构建过表达VASH1的细胞系,以未经感染的细胞为对照;qPCR实验和WB实验检测VASH1的过表达效果,小管形成实验、CCK-8实验、软琼脂克隆形成实验、Transwell实验和划痕愈合实验检测过表达VASH1在体外对细胞的微血管形成、增殖、克隆形成以及迁移能力的影响,NOD-SCID小鼠皮下成瘤实验检测过表达VASH1对SW620细胞移植瘤的体内生长和肺转移的影响。结果： 成功构建过表达VASH1的SW480和SW620细胞。体外实验表明,与对照组相比,过表达VASH1的结直肠癌细胞的微血管形成能力、增殖能力、克隆形成能力以及迁移能力均显著降低（均P<0.05）。体内实验表明,与对照组相比,过表达VASH1的SW620细胞NOD-SCID小鼠皮下移植瘤的生长速度以及肺转移能力也明显降低（均P<0.05）。结论： 过表达VASH1能够抑制人结直肠癌细胞的恶性生物学行为。     

Effect of geniposide on retinal microangiogenesis in rats with diabetic retinopathy and its mechanism北大核心

Objective To investigate the effect of geniposide (Gen) on retinal microangiogenesis in rats with diabetic retinopathy (DR) and its mechanism. Methods Fifty 6-week-old SPF male Wistar rats with normal eyes were randomly divided into the normal group, model group, low-dose Gen group, high-dose Gen group, and calcium dobesilate group, with 10 rats in each group. Except for the normal group, rats in the other groups were fed high-sugar and high-fat diets and induced by streptozotocin to establish the DR rat models. After modeling, drug intervention was carried out immediately. Rats in the low- and high-dose Gen groups were given 25 mg·kg-1 and 100 mg·kg-1 Gen intragastrically, rats in the calcium dobesilate group were given 5.8 mg·kg-1 calcium dobesilate intragastrically, while rats in the normal and model groups were given the same amount of solvent intragastrically, once a day for 4 weeks. During the drug administration period, rats in the normal group continued to be fed normal diets, and rats in the other groups continued to be fed high-sugar and high-fat diets. Levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor 1 (sFlt-1) in serum were measured by the enzyme-linked immunosorbent assay. Retinal pathological changes were exhibited by hematoxylin-eosin staining. Retinal microangiogenesis was revealed by periodic acid-Schiff staining. The expression levels of VEGF, hypoxia-inducible factor-1α (HIF-1α), intercellular adhesion molecule-1 (ICAM-1), and sFlt-1 in the retina were measured by Western blot. Results At the end of drug intervention (week 4), serum VEGF level in the model group was higher than that in the normal group, while sFlt-1 level was lower than that in the normal group (both P<0.001); serum VEGF level in the high-dose Gen and calcium dobesilate groups was lower than that in the model group, while sFlt-1 level was higher than that in the model group (all P<0.001); there were no significant differences in the above indexes between the low-dose Gen group and the model group (all P>0.05). At the end of drug intervention (week 4), the retinal morphology of rats in the normal group was normal, and the cells in the inner and outer nuclear layers were arranged neatly; cells in the inner and outer nuclear layers were arranged loosely, ganglion cells were reduced, and capillary congestion was observed in the model and low-dose Gen groups; the arrangement of cells in the inner and outer nuclear layers in the high-dose Gen and calcium dobesilate groups tended to be normal, and ganglion cells increased compared with the model group. At the end of drug intervention (week 4), the retinal vascular diameter in the model group was uneven, with segmental enlargement, and retinal microangiogenesis was more significant than that in the normal group (P<0.001); retinal microangiogenesis in the high-dose Gen and calcium dobesilate groups was less significant than that in the model group (both P<0.001); there was no significant difference in retinal microangiogenesis between the low-dose Gen group and the model group (P>0.05). At the end of drug intervention (week 4), the relative expression levels of VEGF, HIF-1α and ICAM-1 proteins in the model group were higher than those in the normal group, while the relative expression level of sFlt-1 protein was lower than that in the normal group (all P<0.001); the relative expression levels of VEGF, HIF-1α and ICAM-1 proteins in the high-dose Gen and calcium dobesilate groups were lower than those in the model group, while the relative expression level of sFlt-1 protein was higher than that in the model group (all P<0.001); there were no significant differences in the above indexes between the low-dose Gen group and the model group (all P>0.05). Conclusion Gen can inhibit the expression of VEGF and promote the expression of sFlt-1, which in turn reduces retinal microangiogenesis in DR rats to treat DR. © The Author(s) 2023.