Semen cassiae attenuates myocardial ischemia and reperfusion injury in high-fat diet streptozotocin-induced type 2 diabetic rats.
Obese patients with type 2 diabetes mellitus (T2DM), which is characterized by hyperglycemia, are liable to more severe myocardial infarction. Semen Cassiae is proven to reduce serum lipid levels. This study investigated whether the Semen Cassiae extract (SCE) reduces myocardial ischemia and reperfusion (MI/R) injury with or without diabetes and the underlying mechanisms. The high-fat diet-fed streptozotocin (HFD-STZ) rat model was created as a T2DM model. Normal and DM rats received SCE treatment orally (10 mg/kg/day) for one week. Subsequently these animals were subjected to MI/R. Compared with the normal animals, DM rats showed increased plasma total cholesterol (TC) and triacylglycerol (TG), and more severe MI/R injury and cardiac functional impairment. SCE treatment significantly reduced the plasma TC and TG, improved the instantaneous first derivation of left ventricle pressure and reduced infarct size, decreased plasma creatine kinase and lactate dehydrogenase levels, and apoptosis index at the end of reperfusion in diabetic rats. Moreover, SCE treatment increased the antiapoptotic protein Akt and ERK1/2 phosphorylation levels. Pretreatment with a PI3K inhibitor wortmannin or an ERK1/2 inhibitor PD98059 not only blocked Akt and ERK1/2 phosphorylation respectively, but also inhibited the cardioprotective effects of SCE. However, SCE treatment did not show any effects on the MI/R injury in the normal rats. Our data suggest that SCE effectively improves myocardial function and reduces MI/R-induced injury in diabetic but not normal animals, which is possibly attributed to the reduced TC/TG levels and the triggered cell survival signaling Akt and ERK1/2.
Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China , Experiment Teaching Center, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Feng
F
Fu
Fei
F
Tian
Heping
H
Zhou
Weifeng
W
Lv
Ru
R
Tie
Lele
L
Ji
Rong
R
Li
Zhenwei
Z
Shi
Liming
L
Yu
Xiangyan
X
Liang
Wenjuan
W
Xing
Jinliang
J
Xing
Jun
J
Yu
Lijun
L
Sun
Hailong
H
Zhu
Haifeng
H
Zhang
D000284:Administration, Oral; D000818:Animals; D002366:Cassia / Q000737:chemistry*; D002784:Cholesterol / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000209:etiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D013311:Streptozocin; D014280:Triglycerides / Q000097:blood; D017725:Ventricular Pressure / Q000187:drug effects
D010936:Plant Extracts; D014280:Triglycerides; D013311:Streptozocin; D002784:Cholesterol; D003402:Creatine Kinase