摘要
目的探讨鼠李黄素(Rham)对糖尿病脑梗死大鼠脑组织损伤和炎症反应的影响及相关机制。方法高糖高脂饮食加STZ诱导糖尿病大鼠,线栓法建立T2DM中脑动脉阻塞大鼠模型。将16只建模成功的大鼠随机分为糖尿病脑梗死(MCAO)组和MCAO+Rham组,每组8只。另取16只健康大鼠随机分为正常对照(NC)组和Rham组,每组8只。Rham单日灌胃加药200mg/kg,连续21d。HE染色观察脑组织病理损伤;原位末端标记(TUNEL)法染色检测脑组织细胞凋亡;Westernblot法检测细胞凋亡相关蛋白、c-Jun氨基末端激酶(JNK)及P38的表达;ELISA法检测氧化应激指标和炎症因子的含量。结果与NC组比较,MCAO组脑组织出现明显病理损伤;脑组织细胞凋亡率增加(P<0.01),活化半胱胺酸天冬氨酸蛋白酶3(cleavedcaspase-3)和Bax的表达水平增高,B淋巴细胞癌2(Bcl-2)的表达水平降低(P<0.01);丙二醛(MDA)和一氧化氮(NO)含量升高,SOD活性降低(P<0.01);IL-6、IL-1β和TNF-α的含量升高(P<0.01);p-JNK/JNK和p-P38/P38的比例升高(P<0.01)。与MCAO组比较,MCAO+Rham组脑组织病理损伤减轻;脑组织细胞凋亡率降低(P<0.01);cleavedcaspase-3和Bax的表达水平降低,Bcl-2表达水平升高(P<0.01);MDA和NO的含量降低,SOD活性升高(P<0.01);IL-6、IL-1β和TNF-α含量降低(P<0.01);p-JNK/JNK比例和p-P38/P38比例降低(P<0.01)。结论Rham对糖尿病脑梗死大鼠脑组织损伤和炎症反应具有修复作用,其机制可能与抑制MAPK信号通路活化有关。
Objective To investigate the effects of Rhamnetin (Rham) on brain tissue injury and inflammatory response in diabetic rats with cerebral infarction and its related mechanisms. Methods High glucose and fat diet plus streptozotocin induced diabetic rats were included in this study. Middle cerebral artery occlusion was done to establish type 2 diabetic cerebral infarction rats model (T2DM-MCAO). A total of 16 rats were randomly divided into diabetic cerebral infarction group (MCAO, n = 8) and diabetic cerebral infarction+ Rham group (MCAO+Rham, n = 8). Another 16 healthy rats were randomly divided into healthy control group (NC,n= 8) and Rhamnetin group (Rham, n = 8). Intragastric administration of Rhamnetin 200 mg/kg per day were given for 21 days. Hematoxyli n and easin (HE) staining was used to observe the pathological damage of brain tissue. TUNEL staining was used to detect the apoptosis of brain tissue. Western blot was used to detect the expression of apoptosis related proteins. The content of oxidative stress indicator and inflammatory factor was detect by ELISA. The expression level of JNK and p38 was detected by Western blot. Results Compared with NC group, the brain tissue had obvious pathological damage in MCAO group. The rate of apoptosis in brain tissue was higher, the expression level of cleaved caspase-3 and Bax were higher, the expression level of Bcl-2 was lower, the con tent of MDA and NO were higher (P<0. 01), the ac-tivity of SOD was lower(P<0. 01), the content of IL-6, IL-lβ and TNF-α were higher(P<0. 01), and the ratio of p-JNK/JNK and p-P38/P38 were higher in MCAO group than in NC group(P<0. 01). Compared with MCAO group> the pathological damage of brain tissue was significantly reduced in MCAO+Rham group. The rate of apoptotic cells in the brain tissue was lower, the expression level of cleaved caspase-3 and Bax were lower ,the expression level of Bcl-2 was higher, the content of MDA and NO were lower, the activity of SOD was higher(P<0. 01), the contents of IL-6, IL^1β and TNFp were lower, and the proportion of p-JNK/JNK and p-P38/P38 were lower in MCAO+Rham group than in MCAO group(P<0. 01). Conclusion Rhamnetin has a repair effect on brain tissue injury and inflammatory response in diabetic rats with cerebral infarction, and its mechanism may be related to the inhibition of MAPK signaling pathway activation.
作者
李建设
马玉龙
何文龙
赵剑婷
LI Jianshe;MA Yulong;HE Wenlong(Department of Internal Medicine-Neurology ,Xinriang Central Hospital,Xinjiang 453000,China)
出处
《中国糖尿病杂志》
CAS
CSCD
北大核心
2019年第9期689-694,共6页
Chinese Journal of Diabetes
基金
河南省科技厅重点基金资助项目（XZ5689P90）
关键词
鼠李黄素
糖尿病
脑梗死
炎症反应
氧化应激
Rhamnetin
Diabetes mellitus
Cerebral infarction
Inflammatory reaction
Oxidative stress
