收稿日期: 2025-03-28
网络出版日期: 2025-06-19
基金资助
广东省中医药局项目(20221143);国家中医药传承创新中心科研专项(2022QN04)
Study on the improvement of cardiac and renal function in rats with cardiorenal syndrome by inhibiting fibrosis with 6-gingerol
Received date: 2025-03-28
Online published: 2025-06-19
目的 评估6-姜酚（6-gingerol）抑制纤维化改善心肾综合征大鼠心脏、肾脏功能。 方法 本研究体外实验中，使用同位素标记氨基酸掺入法检测6-姜酚干预大鼠肾脏49F、52E（NRK-49F、NRK-52E）细胞。在体实验将68只200~250 g雄性SD大鼠通过冠状动脉左前降支结扎联合5/6肾次全切除术构建心肾综合征大鼠模型，随机分成对照组、模型组、6-姜酚低剂量组（6 mg/kg）、6-姜酚高剂量组（30 mg/kg）及氯沙坦钾组（20 mg/kg）。6-姜酚组腹腔注射6-姜酚，对照组和模型组给予腹腔注射等量生理盐水，氯沙坦钾组给予灌胃氯沙坦钾共6周。造模成功后取血液行生化、心脏超声等检查，试验结束后取血液、心脏及肾脏行Masson、免疫组化及Western blot等。 结果 6-姜酚20 μmol/L能减少NRK-49F胶原合成和抑制NRK-52E蛋白合成。生化结果显示低、高剂量6-姜酚组及氯沙坦组大鼠的血清肌酐，尿素氮和脑利钠肽（BNP）水平均降低，6-姜酚高剂量组、氯沙坦组大鼠最为显著（P < 0.05）。超声心动图参数显示，6-姜酚组及氯沙坦钾组大鼠改善了心脏收缩功能和心室重构（P < 0.05）。Masson染色和Western-Blot显示肾脏胶原沉积，胶原蛋白I和α-SMA的表达减少（P < 0.05）。免疫荧光提示肾脏胶原沉积I、α-SMA及TGF-β1的表达减少（P < 0.05）。 结论 6-姜酚可通过抑制肾脏纤维化改善心肾综合征大鼠心肾功能。
邓婷 , 傅强 , 李志樑 , 褚庆民 , 周小雄 . 6-姜酚对心肾综合征大鼠心肾功能的影响[J]. 实用医学杂志, 2025 , 41(11) : 1627 -1636 . DOI: 10.3969/j.issn.1006-5725.2025.11.004
Objective To evaluate whether 6-gingerol（6G）can inhibit fibrosis and improve the cardiac and renal function and in rats with cardiorenal syndrome. Methods In the in vitro experiments of this study， the incorporation of isotope-labeled amino acids was used to detect the intervention of 6-gingerol on normal rat kidney-49F （NRK-49F） and normal rat kidney-52E （NRK-52E） cells. 68 male SD rats weighing 200 ~ 250 g were used to establish a rat model of cardiorenal syndrome by ligating the left anterior descending coronary artery and performing 5/6 nephrectomy. The rats were randomly divided into a control group， a model group， a low dose 6-gingerol group （6 mg/kg）， a high dose 6-gingerol group （30 mg/kg）， and a losartan potassium group （20 mg/kg）. The 6-gingerol group received intraperitoneal injection of 6-gingerol， while the control group and model group received intraperitoneal injection of an equal amount of physiological saline. The losartan group received oral administration of losartan potassium for a total of 6 weeks. After successful modeling， blood samples were taken for biochemical and cardiac ultrasound examinations. After the experiment， blood， heart， and kidney samples were taken for Masson， immunohistochemistry， and Western blot. Results 6-gingerol 20 μmol/L can reduce NRK-49F collagen synthesis and inhibit NRK-52E protein synthesis. Biochemical results showed that the serum creatinine， urea nitrogen， and brain natriuretic peptide （BNP） levels of rats in the low and high dose 6-gingerol groups and the losartan group were all reduced， with high dose 6-gingerol groups and losartan group showing the most significant decrease （P < 0.05）. Echocardiographic parameters showed that the 6-gingerol group and losartan potassium group improved cardiac contractile function and ventricular remodeling in rats （P < 0.05）. Masson staining and Western Blot showed renal collagen deposition， with reduced expression of collagen I and α-SMA （P < 0.05）. Immunofluorescence showed a decrease in the expression of renal collagen deposition I， α-SMA， and TGF-β1 （P < 0.05）. Conclusion 6-Gingerol may improve the cardiac and renal function and renal fibrosis in rats with cardiorenal syndrome.
Key words： 6?gingerol; cardiorenal syndrome; fibrosis; cardiac function; renal function
| 1 | RICCI Z， ROMAGNOLI S， RONCO C. Cardiorenal Syndrome［J］. Crit Care Clin， 2021， 37（2）：335-347. doi:10.1016/j.ccc.2020.11.003 |
| 2 | SHAAYA G， AL-KHAZAALI A， ARORA R. Heart Rate As a Biomarker in Heart Failure： Role of Heart Rate Lowering Agents［J］. Am J Ther， 2017， 24（5）：e532-e539. doi:10.1097/mjt.0000000000000336 |
| 3 | SZLAGOR M， DYBIEC J， MLYNARSKA E， et al. Chronic Kidney Disease as a Comorbidity in Heart Failure［J］. Int J Mol Sci， 2023， 24（3）：2988. doi:10.3390/ijms24032988 |
| 4 | CARMENA R， ASCASO J F， REDON J. Chronic kidney disease as a cardiovascular risk factor［J］. J Hypertens， 2020， 38（11）：2110-2121. doi:10.1097/hjh.0000000000002506 |
| 5 | TWARDAWA M， FORMANOWICZ P， FORMANOWICZ D. Chronic Kidney Disease as a Cardiovascular Disorder-Tonometry Data Analyses［J］. Int J Environ Res Public Health， 2022， 19（19）：12339. doi:10.3390/ijerph191912339 |
| 6 | PRICE A M， EDWARDS N C， HAYER M K， et al. Chronic kidney disease as a cardiovascular risk factor： Lessons from kidney donors［J］. J Am Soc Hypertens， 2018， 12（7）：497-505. doi:10.1016/j.jash.2018.04.010 |
| 7 | OTAKI Y， WATANABE T， TAKAHASHI H， et al. Association of renal tubular damage with cardio-renal anemia syndrome in patients with heart failure［J］. Int J Cardiol， 2014， 173（2）：222-228. doi:10.1016/j.ijcard.2014.02.044 |
| 8 | LI W， ZHANG Y， WANG Q， et al. 6-Gingerol ameliorates ulcerative colitis by inhibiting ferroptosis based on the integrative analysis of plasma metabolomics and network pharmacology［J］. Food Funct， 2024， 15（11）：6054-6067. doi:10.1039/d4fo00952e |
| 9 | HAN X， LIU P， LIU M， et al. ［6］-Gingerol Ameliorates ISO-Induced Myocardial Fibrosis by Reducing Oxidative Stress， Inflammation， and Apoptosis through Inhibition of TLR4/MAPKs/NF-kappaB Pathway［J］. Mol Nutr Food Res， 2020， 64（13）：e2000003. doi:10.1002/mnfr.202000003 |
| 10 | YAHYAZADEH R， BARADARAN R V， AHMAD M S， et al. Intra-peritoneal lavage of Zingiber officinale rhizome and its active constituent gingerol impede inflammation， angiogenesis， and fibrosis following post-operative peritoneal adhesion in male rats［J］. Saudi Pharm J， 2024， 32（6）：102092. doi:10.1016/j.jsps.2024.102092 |
| 11 | 石晓路，武乾. 去甲乌药碱与6-姜酚配伍对心衰大鼠强心机制研究［J］. 中华中医药杂志， 2016， 31（2）：420-423. |
| 12 | LIU L， YU N， LENG W， et al. 6-Gingerol， a functional polyphenol of ginger， reduces pulmonary fibrosis by activating Sirtuin1［J］. Allergol Immunopathol （Madr），2022，50（2）：104-114. doi:10.15586/aei.v50i2.533 |
| 13 | ALGANDABY M M， EL-HALAWANY A M， ABDALLAH H M， et al. Gingerol protects against experimental liver fibrosis in rats via suppression of pro-inflammatory and profibrogenic mediators［J］. Naunyn Schmiedebergs Arch Pharmacol， 2016， 389（4）：419-428. doi:10.1007/s00210-016-1210-1 |
| 14 | MA S Q， GUO Z， LIU F Y， et al. 6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway［J］. Acta Pharmacol Sin， 2021， 42（10）：1575-1586. doi:10.1038/s41401-020-00587-z |
| 15 | SONG Z， FANG H， ZHANG X， et al. Renoprotective Glycoside Derivatives from Zingiber officinale （Ginger） Peels［J］. J Agric Food Chem， 2023， 71（41）：15170-15185. doi:10.1021/acs.jafc.3c05224 |
| 16 | SHEN Z， SU T， CHEN J， et al. Collagen triple helix repeat containing-1 exerts antifibrotic effects on human skin fibroblast and bleomycin-induced dermal fibrosis models［J］. Ann Transl Med， 2021， 9（9）：801. doi:10.21037/atm-21-1884 |
| 17 | SHEN Z， SU T， CHEN J， et al. Collagen triple helix repeat containing-1 exerts antifibrotic effects on human skin fibroblast and bleomycin-induced dermal fibrosis models［J］. Ann Transl Med， 2021， 9（9）：801. doi:10.21037/atm-21-1884 |
| 18 | ZHANG Y F， WANG Q， LUO J， et al. Knockdown of elF3a inhibits collagen synthesis in renal fibroblasts via Inhibition of transforming growth factor-beta1/Smad signaling pathway［J］. Int J Clin Exp Pathol， 2015， 8（8）：8983-8989. |
| 19 | LIU S， KOMPA A R， KUMFU S， et al. Subtotal nephrectomy accelerates pathological cardiac remodeling post-myocardial infarction： implications for cardiorenal syndrome［J］. Int J Cardiol， 2013， 168（3）：1866-1880. doi:10.1016/j.ijcard.2012.12.065 |
| 20 | ZHAO R R， ACKERS-JOHNSON M， STENZIG J， et al. Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling［J］. Circulation， 2018， 137（23）：2497-2513. doi:10.1161/circulationaha.117.030353 |
| 21 | YANG K， WANG C， NIE L， et al. Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy［J］. J Am Soc Nephrol， 2015， 26（10）：2434-2446. doi:10.1681/asn.2014060543 |
| 22 | LIU H， ZHU R， LIU C， et al. Evaluation of Decalcification Techniques for Rat Femurs Using HE and Immunohistochemical Staining［J］. Biomed Res Int， 2017， 2017：9050754. doi:10.1155/2017/9050754 |
| 23 | IRIE N， LEE S M， LORENZI V， et al. DMRT1 regulates human germline commitment［J］. Nat Cell Biol， 2023， 25（10）：1439-1452. doi:10.1038/s41556-023-01224-7 |
| 24 | GHOSH-CHOUDHARY S， FINKEL T. Lactylation regulates cardiac function［J］. Cell Res， 2023， 33（9）：653-654. doi:10.1038/s41422-023-00857-5 |
| 25 | SU S A， YANG D， WU Y， et al. EphrinB2 Regulates Cardiac Fibrosis Through Modulating the Interaction of Stat3 and TGF-beta/Smad3 Signaling［J］. Circ Res， 2017， 121（6）：617-627. doi:10.1161/circresaha.117.311045 |
| 26 | ZANNAD F， ROSSIGNOL P. Cardiorenal Syndrome Revisited［J］. Circulation， 2018， 138（9）：929-944. doi:10.1161/circulationaha.117.028814 |
| 27 | DELGADO-VALERO B， CACHOFEIRO V， MARTINEZ-MARTINEZ E. Fibrosis， the Bad Actor in Cardiorenal Syndromes： Mechanisms Involved［J］. Cells， 2021， 10（7）：1824. doi:10.3390/cells10071824 |
| 28 | XU X， ZHANG B， WANG Y， et al. Renal fibrosis in type 2 cardiorenal syndrome： An update on mechanisms and therapeutic opportunities［J］. Biomed Pharmacother， 2023， 164：114901. doi:10.1016/j.biopha.2023.114901 |
| 29 | 曹浩，吉霆威，兰琴，等. 经腹肾次全切建立大鼠心肾综合征模型［J］. 中华医学杂志， 2019， 99（6）：447-452. doi:10.3760/cma.j.issn.0376-2491.2019.06.013 |
| 30 | DENG T， WEI Z， GAEL A， et al. Higenamine Improves Cardiac and Renal Fibrosis in Rats With Cardiorenal Syndrome via ASK1 Signaling Pathway［J］. J Cardiovasc Pharmacol， 2020， 75（6）：535-544. doi:10.1097/fjc.0000000000000822 |
| 31 | QIU Q， CAO J， WANG Y， et al. Time Course of the Effects of Buxin Yishen Decoction in Promoting Heart Function and Inhibiting the Progression of Renal Fibrosis in Myocardial Infarction Caused Type 2 Cardiorenal Syndrome Rats［J］. Front Pharmacol， 2019， 10：1267. doi:10.3389/fphar.2019.01267 |
| 32 | ZHAO Y， WANG C， HONG X， et al. Wnt/beta-catenin signaling mediates both heart and kidney injury in type 2 cardiorenal syndrome［J］. Kidney Int， 2019， 95（4）：815-829. doi:10.1016/j.kint.2018.11.021 |
/
| 〈 |
|
〉 |