CAJ | 학술논문

糖基化终末端产物（AGEs）和4-羟基任烯醛（4-HNE）等活性羰基化合物（Reactive carbonyl compounds， RCCs）激活的RCCs-RAGE（Receptor for AGEs，RAGE）信号轴在糖尿病、神经退行性疾病、癌症等衰退性疾病的发生发展中起了关键性的作用。本研究采用四氧嘧啶腹腔注射的方法建立糖尿病小鼠模型，探讨表没食子儿茶素没食子酸酯（Epigallocatechin Gallate，EGCG）阻抑四氧嘧啶致糖尿病小鼠RCCs-RAGE轴表达的活性。糖尿病小鼠按其体质量与血糖值随机均匀分为模型组、EGCG低剂量组（10 mg·kg-1·d-1）、EGCG中剂量组（20 mg·kg-1·d-1）和 EGCG高剂量组（30 mg·kg-1·d-1）。小鼠连续灌胃 EGCG 12 d后，检测小鼠血清中血糖值、胰岛素和水溶性RAGE（sRAGE）浓度、羰基蛋白含量、AGEs荧光值，QPCR检测肾脏RAGE基因相对表达量，Western blot方法检测肾脏RAGE蛋白和4-HNE含量。结果显示，与糖尿病造模组相比，EGCG通过抑制4-HNE、AGEs 等 RCCs 毒性活性羰基化合物的生成，增加 sRAGE 血清浓度，抑制 AGEs-RAGE 信号轴介导的炎症瀑布反应，有效缓解了机体的氧化应激压力，表现出很好的保护糖尿病小鼠的活性。本研究从一个新角度揭示了EGCG抑制RCCs-RAGE信号轴是其防治衰退性相关疾病的潜在作用机制之一。
당기화종말단산물（AGEs）화4-간기임희철（4-HNE）등활성탄기화합물（Reactive carbonyl compounds， RCCs）격활적RCCs-RAGE（Receptor for AGEs，RAGE）신호축재당뇨병、신경퇴행성질병、암증등쇠퇴성질병적발생발전중기료관건성적작용。본연구채용사양밀정복강주사적방법건립당뇨병소서모형，탐토표몰식자인다소몰식자산지（Epigallocatechin Gallate，EGCG）조억사양밀정치당뇨병소서RCCs-RAGE축표체적활성。당뇨병소서안기체질량여혈당치수궤균균분위모형조、EGCG저제량조（10 mg·kg-1·d-1）、EGCG중제량조（20 mg·kg-1·d-1）화 EGCG고제량조（30 mg·kg-1·d-1）。소서련속관위 EGCG 12 d후，검측소서혈청중혈당치、이도소화수용성RAGE（sRAGE）농도、탄기단백함량、AGEs형광치，QPCR검측신장RAGE기인상대표체량，Western blot방법검측신장RAGE단백화4-HNE함량。결과현시，여당뇨병조모조상비，EGCG통과억제4-HNE、AGEs 등 RCCs 독성활성탄기화합물적생성，증가 sRAGE 혈청농도，억제 AGEs-RAGE 신호축개도적염증폭포반응，유효완해료궤체적양화응격압력，표현출흔호적보호당뇨병소서적활성。본연구종일개신각도게시료EGCG억제RCCs-RAGE신호축시기방치쇠퇴성상관질병적잠재작용궤제지일。
The RCCs-RAGE signal axis induced by RCCs, including AGEs and 4-HNE, plays a key role in degenerative diseases, such as diabetes and cancer. To study on inhibiting activity effects of EGCG on RCCs-RAGE, diabetic mouse induced by intraperitoneal injection Alloxan monohydrate were divided into model group, EGCG-L (10 mg·kg-1·d-1) group, EGCG-M (20 mg·kg-1·d-1) group, and EGCG-H (30 mg·kg-1·d-1) group according to body weight and blood glucose. After 12 days’ administration respectively to three groups of diabetic mouse by gavage, blood glucose value, insulin, sRAGE concentration, carbonyl content and fluorescence value of AGEs in serum were determinde, while the expressions of RAGE gene in kidney were detected by QPCR, RAGE protein and 4-HNE experiment by western bolt. Result showed, compared to model group, EGCG could improve diabetes symptom of mouse by significantly decreasing the formation of RCCs, including carbonyl, 4-HNE and AGEs, increasing the concentration of sRAGE in serum, inhibiting the inflammation reaction induced by RCCs-RAGE, and alleviating the oxidation stress effectively. The study revealed that EGCG inhibited the RCCs-RAGE signal axis may be one of the potential mechanisms in the treatment of degenerative diseases.