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

ABSTRACT

Objective:To study the effect of Suanzaoren Tang on energy metabolism of liver mitochondria in aged rats with chronic rapid eye movement （REM） sleep deprivation. 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 liver mitochondria was observed under the transmission electron microscope. The content of adenosine triphosphate （ATP） in rat liver was detected by colorimetry， and the activities of ubiquinone oxidoreductase （complex Ⅰ）， succinate-ubiquinone oxidoreductase （complex Ⅱ）， ubiquinol-cytochrome c oxidoreductase （complex Ⅲ）， and cytochrome c oxidase （complex Ⅳ） in mitochondrial respiratory chain of rat liver were measured by colorimetry. The protein expression levels of citrate synthase （CS）， isocitrate dehydrogenase （IDH）， and ATP synthase， H⁺ transporting， mitochondrial F0 complex， subunit b， isoform 1 （ATP5F1） in rat liver were assayed by Western blot. Result:The mitochondrial damage in rat liver of the model group was more serious than that in the control group， manifested as mitochondrial swelling and deformation as well as cristae rupture and reduction. The comparison with the model group revealed that both the positive control and Suanzaoren Tang at the high dose obviously alleviated the mitochondrial swelling and deformation and reduced cristae rupture， with better improvements observed in the high-dose Suanzaoren Tang group. Compared with the control group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the model group were all significantly decreased （<italic>P<</italic>0.01）. Compared with the model group， the content of ATP， the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， and Ⅳ， and the protein expression levels of IDH， CS， and ATP5F1 in rat liver of the high-dose Suanzaoren Tang group were all significantly increased （<italic>P<</italic>0.05，<italic>P<</italic>0.01）. In the positive control group， the content of ATP， the activities of mitochondrial respiratory chain complexes I and Ⅲ， and the protein expression levels of CS and ATP5F1 in rat liver were significantly increased （<italic>P<</italic>0.05，<italic> P<</italic>0.01）. The activities of mitochondrial respiratory chain complexes Ⅰ and Ⅲ and the ATP5F1 protein expression in the low-dose Suanzaoren Tang group were significantly elevated （<italic>P<</italic>0.05， <italic>P<</italic>0.01）. Conclusion:Suanzaoren Tang alleviates the abnormal liver energy metabolism induced by chronic REM sleep deprivation in the elderly rats， which may be related to its enhancement of mitochondrial electron transport chain enzyme activities and the up-regulation of protein expression levels of CS， IDH and ATP5F1.