青蒿琥酯干预对伴糖尿病牙周炎大鼠肠道组织TNF-α、 MMP-9及Caspase 3表达的影响

Effect of artesunate intervention on the expression of TNF-α, MMP-9 and Caspase 3 in intestinal tissue of rats with diabetes associated periodontitis

目的研究观察伴糖尿病牙周炎大鼠肠道组织改变情况并探讨青蒿琥酯(artesunate,ART)干预对伴糖尿病牙周炎大鼠肠道组织中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶-9(matrix metallopeptidase-9,MMP-9)及半胱氨酸天冬氨酸蛋白酶3(cysteinecontaining aspartate-specific proteases 3,Caspase 3)的影响。方法选取Sprague-Dawley(SD)大鼠32只,随机分为健康对照组、糖尿病组、伴糖尿病牙周炎组以及ART干预组,进行糖尿病及牙周炎造模并行成模鉴定。第10周末对各组进行干预。ART干预组行60 mg/kg ART灌胃处理,其余各组行生理盐水灌胃处理。第14周末处死大鼠并取肠道组织标本,行HE染色及免疫组织化学染色法检测肠道组织中TNF-α、MMP-9及Caspase 3表达。结果HE染色可见相较于健康对照组,糖尿病组及伴糖尿病牙周炎组肠道上皮肌层损坏,黏膜受损,肠腺变形并伴有淋巴细胞浸润。ART干预组肠道黏膜结构基本完整,肠腺排列较整齐,淋巴细胞浸润减少。糖尿病组、伴糖尿病牙周炎组大鼠TNF-α、MMP-9及Caspase 3表达明显高于健康对照组,差异具有统计学意义(P<0.05);ART干预组较糖尿病组及伴糖尿病牙周炎组TNF-α、MMP-9及Caspase 3表达均显著降低,差异具有统计学意义(P<0.05)。结论伴糖尿病牙周炎大鼠肠道上皮组织有损伤,ART可以通过抑制TNF-α、MMP-9及Caspase 3水平改善肠道组织损伤。

Objective To observe the changes of intestinal tissue in rats with diabetes associated periodontitis and explore the effect of artesunate(ART)intervention on TNF-α,MMP-9 and Caspase 3 in the intestinal tissue of rats with diabetes associated periodontitis.Methods Thirty-two Sprague-Dawley rats were randomly divided into healthy control group,diabetes group,diabetes associated periodontitis group and ART intervention group.Diabetes and periodontitis models were made and model identification was performed.At the end of the 10th week,each group was treated with gavage intervention.Rats in the ART intervention group were treated with 60 mg/kg ART,and other groups were treated with normal saline.At the end of the 14th week,rats were sacrificed and intestinal tissue samples were collected.HE and immunohistochemical staining were processed to detect the expression of TNF-α,MMP-9 and Caspase 3 in intestinal tissues.Results HE staining showed that compared with the healthy control group,the intestinal epithelial muscle layer of the diabetes group and the diabetes associated periodontitis group was damaged;the mucosa was damaged;the intestinal glands were deformed with lymphocyte infiltration.In the ART intervention group,the intestinal mucosa structure was basically complete;the intestinal glands were arranged neatly,and the lymphocyte infiltration was reduced.The expressions of TNF-α,MMP-9 and Caspase 3 in the diabetes group and the diabetes associated periodontitis group were significantly higher than those in the healthy control group(P<0.05).The expressions of TNF-α,MMP-9 and Caspase 3 in the ART intervention group were significantly reduced(P<0.05).Conclusion Diabetes associated periodontitis could damage the intestinal epithelial tissue.ART could restore intestinal tissue damage by inhibiting the levels of TNF-α,MMP-9 and Caspase 3.