Departments of Geriatric, the First Affiliated Hospital, China Medical University, Shenyang, 110001, China.
Department of Radiology, Orthopedic Hospital of Shenyang, Shenyang, 110001, China.
BMC Complement Altern Med. 2018 Jun 22;18(1):192. doi: 10.1186/s12906-018-2257-y.
The Nucleotide binding and oligomerization domain-like receptorfamily pyrin domain-containing 3 (NLRP3)-inflammasome plays an important role in various diseases, including a variety of kidney diseases. Naringin exhibits anti-inflammatory and anti-oxidation effects among others, but its specific mechanisms are not clear. We investigated the expression of the NLRP3-inflammasome under high-glucose conditions, assessed the effects of naringin on that process, and further elucidated the role of naringin in the pathogenesis of diabetic kidney disease(DKD).
To assess the therapeutic potential of naringin and the mechanisms involved, we cultured rat glomerular mesangial cells and grouped them according to different glucose concentrations, different action times, different concentrations of MCC950, and different concentrations of naringin.The cell proliferation was measured by MTT assay. The expression of Interleukin-1β(IL-1β) and Interleukin18 (IL-18) in the cell supernatant were detected by ELISA. The expression and activity of NLPR3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and Caspase-1 were detected by Western Blot.
The expressions of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in rat glomerular mesangial cells were significantly higher in the high glucose (HG) group than in the control normal glucose (NG) group and exhibited time-dependence activity. The expression levels of NLRP3, caspase-1, IL-1β, and IL-18 in different treatment groups were significantly lower compared with the HG group after 48 h of MCC950 pre-treatment (p < 0.05). Pre-treatment with naringin produced the same results. Naringin also inhibited the proliferation of cells.
The NLRP3-inflammasome potentially plays a role in the process of activation and inflammation of glomerular mesangial cells as induced by high-glucose conditions. Naringin inhibited the proliferation of cells that were induced by high glucose. Further, it reduced the expression of inflammatory factors that are mediated by NLRP3 through the NLRP3-caspase-1-IL-1β/IL-18 signaling pathway, which makes naringin a potentially novel treatment for DKD disease.
核苷酸结合寡聚化结构域样受体家族富含半胱氨酸的蛋白 3（NLRP3）炎症小体在各种疾病中发挥重要作用，包括各种肾脏疾病。柚皮苷具有抗炎和抗氧化等作用，但具体机制尚不清楚。我们研究了高糖条件下 NLRP3 炎症小体的表达，评估了柚皮苷对该过程的影响，并进一步阐明了柚皮苷在糖尿病肾病（DKD）发病机制中的作用。
为了评估柚皮苷的治疗潜力及其相关机制，我们培养大鼠肾小球系膜细胞，并根据不同的葡萄糖浓度、不同的作用时间、不同浓度的 MCC950 和不同浓度的柚皮苷进行分组。通过 MTT 法测定细胞增殖。通过 ELISA 检测细胞上清液中白细胞介素 1β（IL-1β）和白细胞介素 18（IL-18）的表达。通过 Western Blot 检测 NLRP3、凋亡相关斑点样蛋白含有半胱氨酸的募集域（ASC）和 Caspase-1 的表达和活性。
高糖（HG）组大鼠肾小球系膜细胞中 NLRP3、ASC、Caspase-1、IL-1β 和 IL-18 的表达明显高于正常葡萄糖（NG）组，且具有时间依赖性活性。MCC950 预处理 48 小时后，不同处理组 NLRP3、Caspase-1、IL-1β 和 IL-18 的表达水平均明显低于 HG 组（p<0.05）。柚皮苷预处理也产生了相同的结果。柚皮苷还抑制细胞增殖。
NLRP3 炎症小体可能在高糖条件下肾小球系膜细胞激活和炎症过程中发挥作用。柚皮苷抑制高糖诱导的细胞增殖。此外，它通过 NLRP3-caspase-1-IL-1β/IL-18 信号通路降低了炎症因子的表达，这使得柚皮苷成为一种潜在的治疗 DKD 的新方法。
