姜黄素类似物H8改善db/db小鼠心肌损伤及其对小鼠神经毒性的影响  

Curcumin Analog H8 Improves Myocardial Injury in db/db Mice and Its Effect on Neurotoxicity in Mice

作　　者：孙文慧 王猛 袁晓环 张哲 SUN Wenhui;WANG Meng;YUAN Xiaohuan;ZHANG Zhe(College of Life Science,Mudanjiang Medical University,Mudanjiang 157011,China)

机构地区：[1]牡丹江医科大学生命科学学院,黑龙江牡丹江157011

出　　处：《中国现代应用药学》2025年第1期54-61,共8页Chinese Journal of Modern Applied Pharmacy

基　　金：牡丹江医学院科学基金火炬计划(2022-MYHJ-006);牡丹江医学院研究生创新科研项目(2019YJSCX-07MY)。

摘　　要：目的研究姜黄素类似物H8对db/db小鼠的心脏损伤改善作用,以及进行H8对小鼠神经毒性的考察。方法将8周龄32只db/db小鼠随机分为模型组、姜黄素组(5 mg·kg^(-1))及其类似物H8低、高剂量组(5、10 mg·kg^(-1)),另取8只db/m小鼠作为正常组,连续灌胃,每日1次,姜黄素及H8用1%CMC-Na溶解。给药8周后,检测空腹血糖(fasting blood glucose,FBG)、乳酸脱氢酶(lactate dehydrogenase,LDH)、肌酸激酶同工酶(creatine kinase isoenzyme,CKMB)、肌酸激酶(creatine kinase,CK)和α-羟丁酸脱氢(α-hydroxybutyrate dehydrogenase,ALPHA-HBDH)水平;HE染色观察心脏组织病理学变化、Masson染色观察纤维化程度;采用Real-time PCR法检测心肌组织中心钠肽(atrial natriuretic peptide,ANP)、脑钠肽(brain natriuretic peptide,BNP)、COL-1、α-SMA、TGF-βmRNA表达水平;采用蛋白免疫印迹法检测心肌组织中COL-1、α-SMA、TGF-β蛋白表达。采用Discovery Studio 2019 tool软件对H8和TGF-βⅡ型受体进行分子对接。随后将48只SPF级ICR小鼠随机分为正常组,H8低、高剂量组(5、10 mg·kg^(-1))。给药12周后检测血清中ALT、AST、AST/ALT水平;进行爬杆试验、鼠尾悬挂试验观察H8是否对正常小鼠产生神经毒性。检查呼吸频率、心跳频率、血压,观察H8是否对正常小鼠产生生理性毒性。结果与正常组比较,模型组小鼠HE染色心脏组织病理学改变,部分心肌细胞变性坏死。同时,Masson染色结果显示,模型组小鼠心肌纤维化程度增加;血清中FBG、LDH、CKMB、CK和ALPHA-HBDH水平升高,差异有统计学意义(P<0.05);心肌组织中ANP、BNP的m RNA表达水平升高,心肌组织中COL-1、α-SMA、TGF-β的mRNA和蛋白表达水平显著增加,差异有统计学意义(P<0.01)。与模型组相比,H8低、高剂量组心肌组织中ANP、BNP mRNA表达水平降低,心肌组织中COL-1、α-SMA、TGF-βmRNA和蛋白表达水平显著减少,差异有统计学意义(P<0.05或P<0.01)。分子对接结果表明H8�OBJECTIVE To study the effect of curcumin analog H8 on the cardiac injury of db/db mice,as well as investigating the neurotoxicity of H8 in mice.METHODS Thirty-two 8-week-old db/db mice were randomly divided into model group,curcumin group(5 mg·kg^(-1))and H8 low and high dose groups(5,10 mg·kg^(-1)),and another 8 db/m mice were regarded as normal group,continuous garage for once a day,curcumin and H8 were dissolved in 1%CMC-Na.After 8 weeks of administration,fasting blood glucose(FBG),lactate dehydrogenase(LDH),creatine kinase isoenzyme(CKMB),creatine kinase(CK)andα-hydroxybutyrate dehydrogenase(ALPHA-HBDH)levels were detected;HE staining was used to observe the pathological changes of cardiac tissue,Masson staining was used to observe the degree of fibrosis;Real-time PCR method was used to detect the atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),COL-1,α-SMA,TGF-βmRNA expression level;Western blotting was used to detect the expression of COL-1,α-SMA,and TGF-βprotein in heart tissue.Molecular docking was used to calculate the sites of H8 and TGF-βII receptor by Discovery Studio 2019 tool software.The 48 SPF ICR mice were randomly divided into normal group,H8 low and high dose groups(5,10 mg·kg^(-1)).After 12 weeks of administration,serum ALT,AST,AST/ALT levels were detected;conduct climbing pole experiment,mice tail suspension experiment to observe whether H8 had neurotoxicity to normal mice.Check respiratory rate,heart rate,blood pressure,and observe whether H8 had physiological toxicity to normal mice.RESULTS Compared with the normal group,the histopathological changes of HE in model group were found,some of the cardiomyocytes became degenerated and necrotic increased.At the same time,Masson staining result showed that the degree of myocardial fibrosis increased in the model group;serum FBG,LDH,CKMB,CK and ALPHA-HBDH levels increased,the difference was statistically significant(P<0.05);the expression levels of ANP and BNP mRNA in myocardial tissue were increased,and the expression leve

关 键 词：姜黄素 姜黄素类似物 2型糖尿病 心肌损伤 神经毒性试验 

分 类 号：R285.5[医药卫生—中药学]