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葡萄籽油对链脲佐菌素-烟酰胺诱导的雄性 2 型糖尿病大鼠肝脏的抗炎、抗凋亡和促增殖作用。

Anti-Inflammatory, Antiapoptotic and Proproliferative Effects of Vitis vinifera Seed Ethanolic Extract in the Liver of Streptozotocin-Nicotinamide-Induced Type 2 Diabetes in Male Rats.

机构信息

Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Can J Diabetes. 2018 Apr;42(2):138-149. doi: 10.1016/j.jcjd.2017.04.005. Epub 2017 Jun 30.

DOI:10.1016/j.jcjd.2017.04.005
PMID:28673757
Abstract

OBJECTIVES

Consumption of Vitis vinifera seed has been reported to ameliorate liver pathology in diabetes mellitus; however, the mechanisms underlying its effects remain unknown. In this study, the anti-inflammatory, anti-apoptotic and pro-proliferative effects of the ethanolic seed extract of V. vinifera (VVSEE) in the liver in cases of diabetes were identified.

METHODS

Adult male rats with streptozotocin-nicotinamide-induced diabetes were given 50, 100 or 200 mg/kg body weight VVSEE orally for 28 days. At the end of the treatment, body weights were determined, and the blood was collected for analyses of fasting blood glucose, insulin and liver enzyme levels. Following sacrifice, livers were harvested and their wet weights and glycogen contents were measured. Histologic appearances of the livers were observed under light microscopy, and the expression and distribution of inflammatory, apoptosis and proliferative markers in the livers were identified by molecular biologic techniques.

RESULTS

Treatment of rats with diabetes by VVSEE attenuates decreased body weight, liver weight and liver glycogen content. Additionally, increases in fasting blood glucose levels and liver enzyme levels and decreases in serum insulin levels were ameliorated. Lesser histopathologic changes were also observed: decreased inflammation and apoptosis, as indicated by decreased levels of inflammatory markers (TNF-α, NF-Kβ, IKK-β, IL-6, IL-1β) and apoptosis markers (caspase-3, caspase-9 and Bax). VVSEE treatment induces increase in hepatocyte regeneration, as indicated by increased PCNA and Ki-67 distribution in the livers of rats with diabetes. Several molecules identified in VVSEE via gas chromatography mass spectrometry might contribute to these effects.

CONCLUSIONS

The anti-inflammatory, anti-apoptotic and pro-proliferative effects of VVSEE could account for its hepatoprotective actions in diabetes.

摘要

目的

有报道称,葡萄(Vitis vinifera)籽的摄入可改善糖尿病患者的肝病理学;然而,其作用机制尚不清楚。在本研究中,鉴定了葡萄籽乙醇提取物(VVSEE)在糖尿病情况下对肝脏的抗炎、抗凋亡和促增殖作用。

方法

用链脲佐菌素-烟酰胺诱导的糖尿病雄性成年大鼠经口给予 50、100 或 200mg/kg 体重的 VVSEE,共 28 天。在治疗结束时,测定体重,并采集血液分析空腹血糖、胰岛素和肝酶水平。处死大鼠后,采集肝脏并测量其湿重和糖原含量。用光学显微镜观察肝脏的组织学外观,并通过分子生物学技术鉴定肝脏中炎症、凋亡和增殖标志物的表达和分布。

结果

VVSEE 治疗糖尿病大鼠可减轻体重、肝重和肝糖原含量的降低。此外,还改善了空腹血糖水平和肝酶水平的升高以及血清胰岛素水平的降低。还观察到较小的组织病理学变化:炎症标志物(TNF-α、NF-Kβ、IKK-β、IL-6、IL-1β)和凋亡标志物(caspase-3、caspase-9 和 Bax)水平降低,表明炎症和凋亡减少。VVSEE 治疗诱导肝再生增加,糖尿病大鼠肝脏中 PCNA 和 Ki-67 的分布增加表明这一点。通过气相色谱质谱联用仪鉴定的 VVSEE 中的几种分子可能有助于这些作用。

结论

VVSEE 的抗炎、抗凋亡和促增殖作用可能解释了其在糖尿病中的肝保护作用。

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