Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats.
Naringin inhibits vascular endothelial cell apoptosis via endoplasmic reticulum stress‑ and mitochondrial‑mediated pathways and promotes intraosseous angiogenesis in ovariectomized rats.
复制标题
DOI：
10.3892/ijmm.2017.3160
复制
发表时间：
2017-12
影响因子：
5.4
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Shangguan WJ;Zhang YH;Li ZC;Tang LM;Shao J;Li H
为探讨柚皮苷对血管内皮细胞功能、增殖、凋亡和血管生成的影响，将体外培养的大鼠血管内皮细胞随机分为4组：对照组、血清饥饿组、低浓度柚皮苷组和高浓度柚皮苷组。MTT法检测细胞增殖，Hoechst 33258染色和流式细胞术检测细胞凋亡。使用蛋白质印迹法检测凋亡相关蛋白[GRP 78、CHOP、caspase-12和细胞色素c（Cyt.c）]表达的变化。JC-1染色检测线粒体膜电位的变化。用分光光度法测定细胞内caspase-3、-8和-9活性。采用ELISA法检测内皮素（ET），Griess法检测培养液中一氧化氮（NO）的表达变化。本研究进一步将去卵巢（OVX）骨质疏松大鼠模型随机分为4组：去卵巢组、假手术组、低浓度柚皮苷治疗组（100 mg/kg）和高浓度柚皮苷治疗组（200 mg/kg）。治疗3个月后，测定血清ET和NO表达、骨密度（BMD）和股骨远端微血管密度（使用VECs的CD 34标记）的变化。在每个浓度下，柚皮苷促进VEC增殖的时间和剂量依赖性的方式。柚皮苷还显著降低血清饥饿诱导的内皮细胞凋亡，抑制GRP 78、CHOP、caspase-12和Cyt.c蛋白的表达，降低线粒体膜电位，并降低caspase-3和-9的活性。此外，柚苷抑制ET在体外和体内，而增加NO的合成。股骨远端微血管密度评估显示，柚苷治疗组的微血管数量显着高于OVX组，且微血管密度与BMD正相关。总之，柚苷通过阻断内质网（ER）应激和内质网介导的途径抑制血管内皮细胞凋亡。柚苷还可调节内皮细胞功能，促进血管生成，发挥其抗肿瘤作用。
In this study, to investigate the effects of naringin on vascular endothelial cell (VEC) function, proliferation, apoptosis, and angiogenesis, rat VECs were cultured in vitro and randomly divided into four groups: control, serum-starved, low-concentration naringin treatment, and high-concentration naringin treatment. MTT assay was used to detect cell proliferation while Hoechst 33258 staining and flow cytometry were used to detect apoptosis. Changes in the expression of apoptosis-associated proteins [GRP78, CHOP, caspase-12, and cytochrome c (Cyt.c)] were detected using western blotting. JC-1 staining was employed to detect changes in mitochondrial membrane potential. Intracellular caspase-3, -8, and -9 activity was determined by spectrophotometry. ELISA was used to detect endothelin (ET), and a Griess assay was used to detect changes in the expression of nitric oxide (NO) in culture medium. The study further divided an ovariectomized (OVX) rat model of osteoporosis randomly into four groups: OVX, sham-operated, low-concentration naringin treatment (100 mg/kg), and high-concentration naringin treatment (200 mg/kg). After 3 months of treatment, changes in serum ET and NO expression, bone mineral density (BMD), and microvessel density of the distal femur (using CD34 labeling of VECs) were determined. At each concentration, naringin promoted VEC proliferation in a time- and dose-dependent manner. Naringin also significantly reduced serum starvation-induced apoptosis in endothelial cells, inhibited the expression of GRP78, CHOP, caspase-12, and Cyt.c proteins, and reduced mitochondrial membrane potential as well as reduced the activities of caspase-3 and -9. Furthermore, naringin suppressed ET in vitro and in vivo while enhancing NO synthesis. Distal femoral microvascular density assessment showed that the naringin treatment groups had a significantly higher number of microvessels than the OVX group, and that microvascular density was positively correlated with BMD. In summary, naringin inhibits apoptosis in VECs by blocking the endoplasmic reticulum (ER) stress- and mitochondrial-mediated pathways. Naringin also regulates endothelial cell function and promotes angiogenesis to exert its anti-osteoporotic effect.
登录
查看更多内容
影响因子：
4.3
作者：
Byon, Chang Hyun;Chen, Yabing
通讯作者：
Chen, Yabing
影响因子：
20.3
作者：
Padró, T;Ruiz, S;Mesters, RM
通讯作者：
Mesters, RM
影响因子：
5
作者：
Peng-Zhang;Dai, Ke-rong;Xu, Zhan-wang
通讯作者：
Xu, Zhan-wang
影响因子：
2.7
作者：
Kumar, Puneet;Kumar, Anil
通讯作者：
Kumar, Anil
DOI：
10.3109/10623329909165310
发表时间：
1999-01-01
影响因子：
--
作者：
Hogg, N;Browning, J;Gobé, G
通讯作者：
Gobé, G