Effect of Suanzaoren Tang on Energy Metabolism of Myocardial Mitochondria in Aged Rats with Chronic Rapid Eye Movement Sleep Deprivation / 中国实验方剂学杂志

ABSTRACT

Objective:To study the mechanism of Suanzaoren Tang in regulating the energy metabolism of myocardial mitochondria in aged rats with chronic rapid eye movement （REM） sleep deprivation through the sirtuin 3 （SIRT3）/superoxide dismutase2 （SOD2） signaling pathway. Method:Fifty male Wistar rats were randomly divided into the control group， model group， estazolam group （0.18 mg·kg^-1·d^-1）， and low- （6.48 g·kg^-1·d^-1） and high-dose （12.96 g·kg^-1·d^-1） Suanzaoren Tang groups. Rats in all groups except for the control group received subcutaneous injection of <italic>D</italic>-galactose and then were deprived of sleep using the multiple platform method after the last administration. Following successful modeling， the rats in each group were treated with intragastric administration of the corresponding drugs for seven consecutive days. The morphology of myocardial mitochondria was observed under a transmission electron microscope. The content of adenosine triphosphate （ATP） in rat hypothalamus was detected by colorimetry， while the malondialdehyde （MDA） content and the SOD activity in myocardium were measured by spectrophotometry. Real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to determine the mRNA and protein expression levels of SIRT3 and SOD2 in rat myocardium. The localization of SIRT3 was detected by immunofluorescence staining. Result:Compared with the control group， the model group exhibited a disordered arrangement of myocardial filaments， accompanied by filament rupture and dissolution， obviously swollen mitochondria arranged in disorder， and blurring and even rupture of most mitochondrial cristae. Besides， the content of ATP and SOD activity in the myocardium decreased significantly （<italic>P<</italic>0.01）， whereas that of MDA increased significantly （<italic>P<</italic>0.01）. The mRNA and protein expression levels of SIRT3 and SOD2 were down-regulated significantly （<italic>P<</italic>0.01）， and the average fluorescence intensity of SIRT3 protein declined significantly （<italic>P<</italic>0.01）. The comparison with the model group revealed that high-dose Suanzaoren Tang enabled the myocardial filaments to be neatly arranged， relieved the mitochondrial damage and swelling， only manifested as partial mitochondrial cristae rupture， significantly increased ATP content， SOD activity， as well as SIRT3 and SOD2 mRNA and protein expression levels （<italic>P<</italic>0.01）， reduced the content of MDA （<italic>P<</italic>0.01）， and enhanced the average fluorescence intensity of SIRT3 protein （<italic>P<</italic>0.05）. The myocardial mitochondrial injury in the estazolam group was also alleviated. The activity of SOD and the SIRT3 and SOD2 mRNA and protein expression levels in the myocardium were significantly elevated （<italic>P<</italic>0.01）， while the activity of MDA was significantly lowered （<italic>P<</italic>0.01）. In the low-dose Suanzaoren Tang group， the improvement in myocardial mitochondrial injury was not obvious. However， both the SOD activity and SOD2 protein expression were significantly increased （<italic>P<</italic>0.05）. Conclusion:Suanzaoren Tang ameliorates the myocardial mitochondria injury and abnormal energy metabolism induced by chronic REM sleep deprivation in aged rats possibly by up-regulating the SIRT3 and SOD2 expression.