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[Protective effect of safflower yellow injection against rat MIRI by TLR-NF-κB inflammatory pathway]
Ling-Mei Li1, Jian-Hua Fu1, Hao Guo2
1School of Integrated Traditional Chinese and Western Medicine,Binzhou Medical University Yantai 264003,China Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences Beijing 100091,China.
Abstract:
This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.
Insights
Safflower yellow injection significantly reduces myocardial ischemia-reperfusion injury (MIRI) in rats by inhibiting inflammatory responses. This effect is linked to regulating the Toll-like receptor 4 (TLR4)-nuclear factor-kappa B (NF-κB) pathway.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Cellular Biology
Background:
- Myocardial ischemia-reperfusion injury (MIRI) is a critical condition leading to significant heart damage.
- Inflammatory responses play a key role in the pathogenesis of MIRI.
- Novel therapeutic strategies targeting inflammation are needed to mitigate MIRI-induced damage.
Purpose of the Study:
- To investigate the protective mechanism of safflower yellow injection against MIRI in a rat model.
- To elucidate the role of the Toll-like receptor 4 (TLR4)-nuclear factor-kappa B (NF-κB) pathway in safflower yellow's anti-MIRI effects.
Main Methods:
- Establishment of a MIRI rat model by ligating the left anterior descending coronary artery.
- Histopathological analysis (HE staining) and infarct size measurement (TTC staining).
- Biochemical assays and ELISA for inflammatory markers (TNF-α, IL-6) and cardiac enzymes (CK, AST, LDH).
- Western blot to assess protein expression of TLR4 and NF-κB p65.
Main Results:
- MIRI induced significant myocardial damage, inflammation, elevated cardiac enzymes, and increased TLR4/NF-κB expression.
- Safflower yellow injection dose-dependently reduced infarct size, edema, inflammatory markers, and cardiac enzyme levels.
- Treatment with safflower yellow injection decreased the expression of TLR4 and NF-κB p65 in myocardial tissues.
Conclusions:
- Safflower yellow injection demonstrates significant protective effects against MIRI in rats.
- The mechanism involves the regulation of the TLR4-NF-κB signaling pathway, thereby inhibiting the inflammatory response.
- Safflower yellow injection represents a potential therapeutic agent for MIRI.
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