Protective Effect Of Sequoyitol On Myocardial Injury In Type2Diabetic Rats And The Potential Mechanisms

Objective: To observe the protective effect of sequoyitol on myocardial injuries in type2diabetic rats and explore its mechanism.Methods:60male SD rats were randomly divided into normal control group (distilledwater,5.0ml·kg-1·d-1,n=7) and diabetic model group (53), Type2diabetic rats modelwas established by intraperitoneal injection with a single dose of streptozotocin (STZ,35mg/kg) and fed with a high-fat high-sucrose diet. The model rats were randomlydivided into type2diabetic rats (distilled water5ml·kg-1·d-1) group, Sequoyitol (12.5,25, and50mg·kg-1·d-1, respectively) groups, and Acarbose (20mg·kg-1·d-1) group. Allgroups were fed with these dosages daily for6weeks. Fasting glucose was measuredevery2weeks before and during administration.Body weight was recorded for6weeksfortnightly interval with all animals. After6weeks, collected blood from abdominalaortas.Heart was weighed and heart weight index was calculated respectively. Theserum lactate dehydrogenase (LDH), phosphocreatine kinase (CRK) and C-reactiveprotein (CRP) were determined by ELISA. Morphological change was observed by HEand Masson staining. The level of NO in myocardium was detected by nitrate reduction.Sulfur thiobarbituric acid assay MDA content in myocardial tissue.The levels ofT-AOC, SOD, and H2O2in myocardium were detected by colorimetry. The expressionsof inducible nitric oxide synthase (iNOS) protein in myocardium were determined byimmunohistochemisty.Level of tumor necrosis factor α(TNF)-α in serum wasdetermined by ELISA.The expression of iNOS mRNA in myocardium was observed by RT-PCR. In addition, the expressions of NADPH oxidase p22phox, p47phox, andinducible nitric oxide synthase (iNOS) protein in myocardium were determined byWestern blot.Results:(1) Compared with the normal control group, fasting blood glucose of model group wassignificantly increased(P<0.01).Compared with the model group, after4weeks ofadministration, fasting blood glucose were significantly decreased in sequyitol groupsor acarbose group (P<0.05or P<0.01).(2) Compared with the normal control group, the levels of serum CK, LDH, C-reactiveprotein and TNF-α were significantly increased in model group (P<0.01).Comparedwith the model group,the levels of serum CK, LDH, C-reactive protein and TNF-α ofsequoyitol groups or acarbose group were significantly decreased(P<0.05or P<0.01).(3) Compared with the normal control group, the body weight was significantlydecreased and heart weight index was obviously increased in diabetic rats (P<0.01),which was attenuated by treatment with sequoyitol or acarbose.(4) HE staining and Masson staining showed that the myocardial cell hypertrophy anddisorganized, enlarged nuclei stained nucleus visible degeneration, myocardial cell gapwidened, a large organization can be seen inflammatory cells and adipose tissueinfiltration, interstitial myocardial and vascular beside a clear blue stained myocardialinterstitial and perivascular fibrous tissue was significantly increased and disorganized,with severe collagen deposition in in the model group. All these effect weresignificantly alleviated by treatment of rats with sequoyitol or acarbose.(5) Compared with the normal control group, the levels of myocardial NO, MDA,H2O2were significantly increased and T-AOC, SOD were obviously decreased(P<0.01) in type2diabetic rats. Compared with the model group, the levels ofmyocardial NO, MDA, H2O2were significantly decreased and T-AOC,SOD wereobviously increased in sequoyitol group or acarbose group (P<0.05or P<0.01). (6) Compared with the normal control group, the expression of iNOS mRNA andprotein in myocardial tissue of model group were significantly increased(P<0.01).Compared with the model group, sequoyitol or acarbose obviouslydown-regulated the expression of iNOS mRNA and protein in myocardial tissue(P<0.05or P<0.01).(7) Compared with the normal control group, the expression of p22phox, p47phoxprotein inmyocardial tissue of model group were significantly increased (P<0.01).Comparedwith the model group, sequoyitol or acarbose obviously down-regulated the expressionof p22phox, p47phoxin myocardial tissue (P<0.05or P<0.01).Conclusions:(1) Sequoyitol can significantly reduce fasting blood glucose.(2) Sequoyitol can significantly decrease the levels of serum LDH, CPK, C-reactiveprotein and TNF-α in type diabetic rats.(3) Sequoyitol also significantly reduced myocardial remodeling and collagendeposition in type2diabetic rats.(4) Sequoyitol significantly decreased the levels of myocardial NO, MDA, H2O2andobviously increased T-AOC, SOD in type2diabetic rats.(5) Sequoyitol obviously down-regulate the expression of iNOS mRNA and iNOS,P22phox, P47phoxprotein in myocardial tissue of type2diabetic rats.