Forsythiaside A alleviates myocardial injury in streptozotocin-induced diabetes via endoplasmic reticulum stress-NLRP3 inflammasome pathway

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-02-06 DOI:10.1016/j.intimp.2024.113956

Chuanpu Shen , Qing Zhang

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Abstract

The aim of this study was to evaluate for the effects of forsythiaside A (FA) on myocardial injury in streptozotocin (STZ)-induced diabetes mice. Blood glucose (BG), serum triglycerides (TG), lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), cardiac troponin (cTnI), malondialdehyde (MDA), superoxide dismutase (SOD) levels were detected in STZ mice. The structure and function of heart was observed via cardiac ultrasound. Cytokine levels in mouse serum and heart were detected using enzyme-linked immunosorbent assay (ELISA) as well as TG, LDH, CK-MB, cTnI, MDA and SOD in high glucose (Glu) induced H9c2 cells. Western blot detection of the expression of endoplasmic reticulum stress-related TXNIP/NLRP3 inflammasome pathways (GRP78, PERK, P-PERK, EIF-α, P-EIF-α, XBP1, ATF6, TXNIP and NLRP3) in SCD mice and LCG induced H9c2 cells. Endoplasmic reticulum stress activator tunicamycin (TM) was used to validate the above pathway for FA. It was also found that FA had protective effects on myocardial injury in STZ mice via restored heart function, improved cardiac pathological changes and suppressed inflammatory response as well as in Glu induced H9c2 cells. In conclusion, FA alleviated myocardial injury in diabetes via endoplasmic reticulum stress-NLRP3 inflammasome pathway.

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连翘苷A通过内质网应激- nlrp3炎性体通路减轻链脲佐菌素诱导糖尿病心肌损伤。

本研究旨在探讨连翘苷A （FA）对链脲佐菌素（STZ）诱导的糖尿病小鼠心肌损伤的影响。检测STZ小鼠血糖（BG）、血清甘油三酯（TG）、乳酸脱氢酶（LDH）、肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白（cTnI）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平。通过心脏超声观察心脏的结构和功能。采用酶联免疫吸附法（ELISA）检测小鼠血清和心脏细胞因子水平，以及高糖（Glu）诱导的H9c2细胞TG、LDH、CK-MB、cTnI、MDA和SOD水平。Western blot检测SCD小鼠和LCG诱导的H9c2细胞内质网应激相关TXNIP/NLRP3炎症小体通路（GRP78、PERK、P-PERK、EIF-α、P-EIF-α、XBP1、ATF6、TXNIP和NLRP3）的表达。利用内质网应激激活剂tunicamycin （TM）验证上述FA通路。还发现FA通过恢复心功能、改善心脏病理改变、抑制炎症反应以及Glu诱导的H9c2细胞对STZ小鼠心肌损伤具有保护作用。综上所述，FA可通过内质网应激- nlrp3炎症体途径减轻糖尿病心肌损伤。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.