返回 
加入收藏
延胡索总生物碱对糖尿病心肌病大鼠铜死亡的调控作用及机制
x
请在关注微信后，向客服人员索取文件
| 篇名： | 延胡索总生物碱对糖尿病心肌病大鼠铜死亡的调控作用及机制 |
| TITLE： | Effects and mechanism of total alkaloids of Corydalis Rhizoma on the regulation of cuproptosis in rats with diabetic cardiomyopathy |
| 摘要： | 目的 基于沉默信息调节因子1（Sirt1）/肿瘤抑制因子53（P53）信号通路，探讨延胡索总生物碱（TAC）对糖尿病心肌病（DCM）大鼠铜死亡的调控作用及机制。方法采用高脂高糖饲料喂养+腹腔注射链脲佐菌素建立DCM大鼠模型。取32只造模成功的大鼠随机分为模型组和TAC低、中、高剂量组（7、10.5、14mg/kg），每组8只。另取8只大鼠以正常饲料喂养作为正常对照组。各组大鼠灌胃相应药物或生理盐水，每天1次，连续4周。末次给药后，检测大鼠空腹血糖（FBG）水平；检测大鼠血清和心肌组织中肌酸激酶（CK）、CK同工酶MB（CK-MB）、乳酸脱氢酶（LDH）水平；观察大鼠心肌组织病理学形态、纤维化程度及Cu2+沉积情况；检测大鼠心肌组织中Cu2+、谷胱甘肽（GSH）水平以及Sirt1/P53信号通路相关蛋白[Sirt1、P53、溶质家族载体7成员11（SLC7A11）]、铁硫簇相关蛋白[铁氧还蛋白1（FDX1）、硫辛酸合成酶（LIAS）、线粒体乌头酸酶2（ACO2）、泛醌氧化还原酶核心亚基S8（NDUFS8）、二氢硫辛酸乙酰基转移酶（DLAT）、二氢硫辛酸二酰基转移酶（DLST）]、热休克蛋白70（HSP70）表达水平。结果与正常对照组相比，模型组大鼠FBG水平，血清和心肌组织中CK、CK-MB、LDH水平，心肌组织中Cu2+水平以及P53、HSP70蛋白表达水平均显著升高（P＜0.05）；心肌组织中GSH水平和Sirt1、SLC7A11、FDX1、LIAS、ACO2、NDUFS8、DLAT、DLST蛋白表达水平均显著降低（P＜0.05）；心肌组织病理损伤严重，出现较多炎症细胞浸润，且纤维化明显，Cu2+沉积增多。与模型组比较，TAC各剂量组大鼠上述大部分定量指标均显著逆转（P＜0.05）；心肌组织病理损伤减轻，纤维化和Cu2+沉积减少。结论TAC可改善大鼠DCM，其作用机制可能与激活Sirt1/P53信号通路活性，促进GSH与Cu2+的螯合作用，抑制心肌细胞铜死亡有关。 |
| ABSTRACT： | OBJECTIVE To investigate the effects and mechanism of total alkaloids of Corydalis Rhizoma （TAC） on the regulation of cuproptosis in rats with diabetic cardiomyopathy （DCM） based on silence information regulator 1（Sirt1）/tumor protein 53（P53）signaling pathway. METHODS DCM rat model was induced by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. Thirty-two model rats were randomly divided into model group， TAC low-dose， medium-dose and high-dose groups （7， 10.5， 14 mg/kg）， with 8 rats in each group. An additional 8 rats were assigned to normal control group. Related drugs or normal saline were administered intragastrically in each group， once a day， for 4 weeks. After the last medication， the fasting blood glucose （FBG） levels of the rats were measured. The levels of myocardial creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in serum and myocardial tissue of rats were all detected. The pathological morphology， fibrosis degree， and Cu2+ deposition of myocardial tissue in rats were observed. The levels of Cu2+ and glutathione （GSH） in myocardial tissue， the expressions of Sirt1/P53 signaling pathway-related proteins [Sirt1， P53， solute carrier family 7 membrane 11 （SLC7A11）]， and iron-sulfur cluster-related proteins [ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， aconitase 2 （ACO2）， NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）， dihydrolipoamide acetyltransferase （DLAT）， dihydrolipoamide succinyltransferase （DLST）]， and heat shock protein 70 （HSP70） were all determined. RESULTS Compared with normal control group， the model group exhibited significantly elevated levels of FBG， CK， CK-MB and LDH in both serum and myocardial tissue， as well as increased 2+ levels of Cu in myocardial tissue and the expression of P53 and HSP70 proteins （P＜0.05）； the level of GSH and the expression levels of Sirt1， SLC7A11， FDX1， LIAS， ACO2， NDUFS8， DLAT， and DLST proteins in myocardial tissue were all significantly decreased （P＜0.05）； the myocardial tissue exhibited severe pathological damage， with numerous inflammatory cell infiltrations and significant fibrosis， as well as increased deposition of Cu2+. Compared with model group， most of the above quantitative indicators in rats were significantly reversed in TAC groups （P＜0.05）； the pathological damage to the myocardial tissue was alleviated， with reduced fibrosis and Cu2+ deposition. CONCLUSIONS TAC can ameliorate DCM in rats， and its mechanism of action may be related to activating the activity of the Sirt1/P53 signaling pathway， promoting the chelation of GSH with Cu2+， and inhibiting cuproptosis of cardiomyocyte. |
| 期刊： | 2025年第36卷第07期 |
| 作者： | 李君；齐雅芝；唐娅；曹睿；徐强；韩玉生 |
| AUTHORS： | LI Jun，QI Yazhi，TANG Ya，CAO Rui，XU Qiang，HAN Yusheng |
| 关键字： | 延胡索总生物碱；糖尿病心肌病；铜死亡；Sirt/P53信号通路；铁硫簇 |
| KEYWORDS： | total alkaloids of Corydalis Rhizoma； diabetic cardiomyopathy； cuproptosis； Sirt1/P53 signaling pathway； iron- |
| 阅读数： | 6 次 |
| 本月下载数： | 0 次 |
* 注：未经本站明确许可，任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作！
