| 引用本文: | 张哲.姜黄素类似物H8改善db/db小鼠心肌损伤及对药物的安全性评价[J].中国现代应用药学,2025,42(1):9-8. |
| zhangzhe.Curcumin Analog H8 Improves Myocardial Injury in db/db Mice with SafetySun Wenhui1, Wang Meng1, Yuan Xiaohuan1,Zhang zhe1* (1. College of Life Science, Mudanjiang Medical College, Mudanjiang 157011, China)[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(1):9-8. |
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| 姜黄素类似物H8改善db/db小鼠心肌损伤及对药物的安全性评价 |
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张哲
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牡丹江医学院
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| 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的安全性评价。方法 将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。8周后检测血清中葡萄糖(FBG),乳酸脱氢酶 (LDH),肌酸激酶同工酶(CKMB),肌酸激酶(CK)和α-羟丁酸脱氢(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-timePCR法检测心肌组织中心钠肽(ANP)、脑钠肽(BNP)、COL-1、α-SMA、TGF-β mRNA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-β Ⅱ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( 2.5,10)mg.kg-1。12 周后检测血清中ALT,AST,AST/ALT水平；进行爬杆实验、鼠尾悬挂实验观察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,Masson染色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mRNA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)。与模型组比较,姜黄素组血清中CKMB水平降低,差异有统计学意义(P＜0.05)；染色结果表明H8组心肌细胞病理学改变和纤维化程度明显减轻；血清中FBG,LDH,CK,ALPHA-HBDH水平明显降低,差异统计学意义(P＜0.01)。心肌组织中ANP、BNP mRNA表达水平降低,心肌组织中COL-1、α-SMA、TGF-β mRNA和蛋白表达水平显著减少,差异有统计学意义(P＜0.01)。分子对接结果表明H8可以和TGF-β Ⅱ型受体形成氢键。与正常组比较,给药组小鼠血清中ALT,AST,AST/ALT水平,小鼠爬杆情况、鼠尾悬挂时间没有明显差别,差异无统计学意义(P＞0.05)。与正常组比较,给药组小鼠呼吸频率、心跳频率和血压没有明显差别,差异无统计学意义(P＞0.05)。结论: 姜黄素及其类似物 H8可以改善db/db小鼠的心脏损伤及未对实验小鼠产生明显的毒性作用。 |
| 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 |
| DOI： |
| 分类号:R284.1；R917.101 |
| 基金项目:牡丹江医学院科学基金火炬计划, |
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| Curcumin Analog H8 Improves Myocardial Injury in db/db Mice with SafetySun Wenhui1, Wang Meng1, Yuan Xiaohuan1,Zhang zhe1* (1. College of Life Science, Mudanjiang Medical College, Mudanjiang 157011, China) |
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zhangzhe
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Mudanjiang medical university
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| Abstract: |
| ABSTRACT: OBJECTIVE To study the effect of curcumin analog H8 on the cardiac injury of db/db mice and the safety evaluation of H8. METHODS Thirty-two 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. After 8 weeks, serum glucose (FBG), lactate dehydrogenase (LDH), creatine kinase isoenzyme (CKMB), creatine kinase (CK) and α-hydroxybutyrate dehydrogenase (ALPHA-HBDH) levels were detected; HE staining to observe the pathological changes of cardiac tissue, Masson staining to observe the degree of fibrosis; Real-time PCR method was used to detect the central natriuretic peptide (ANP), brain natriuretic peptide (BNP), COL-1, α-SMA, TGF-β mRNA expression level; Western blotting was used to detect the expression of COL-1, α-SMA, and TGF-β protein in heart tissue. Molecular docking was used to calculate the sites of H8 and TGF-β II receptor. 48 SPF ICR mice were randomly divided into normal group, H8 low, medium and high dose groups (2.5, 10) mg?kg-1. After 12 W, serum ALT, AST, AST/ALT levels were detected; Conduct climbing pole experiment, rat tail suspension experiment to observe whether H8 has neurotoxicity to mice. RESULTS Compared with the normal group, the histopathological changes of HE in model group were found, increased myocardial fibrosis in Masson staining were detected; 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 increased, and the expression levels of COL-1, significant (P<0.01). Compared with the model group, the serum CKMB level in the curcumin group decreased, the α-SMA, TGF-β mRNA and protein in myocardial tissue increased significantly, and the difference was statistically significant (P＜0.05), the H8 group myocardial cell pathological changes and the difference was statistically degree of fibrosis were significantly reduced; Serum FBG, LDH, CK, ALPHA-HBDH level was significantly reduced, and the difference was statistically significant (P<0.01). The expression levels of ANP and BNP mRNA in myocardial tissue decreased, and the expression levels of COL-1, α-SMA, TGF-β mRNA and protein in myocardial tissue inhibited significantly, and the difference was statistically significant (P<0.01). Molecular docking results indicate that H8 can interact with TGF-β receptor with hydrogen bonds. Compared with the normal group, there were no significant differences in serum ALT, AST, AST/ALT levels, rod climbing conditions and tail suspension time in the administration group, and the differences were not statistically significant (P>0.05). CONCLUSION Curcumin and its analogue H8 can improve the heart injury of db/db mice and have no obvious neurotoxic effect on experimental mice. |
| Key words: curcumin curcumin analogs type 2 diabetes myocardial injury neurotoxicity test |
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