Abstract
OBJECTIVE:To study whether Shenshuai recipe(肾衰方,SSR)can play a protective role on chronic kidney disease myocardial injury model through phosphatase and tensin homolog-induced putative kinase 1(PINK1)/E3 ubiquitin ligase Parkin(Parkin)mitochondrial autophagy pathway.METHODS:Forty-eight nephrectomized rats were randomly divided into six groups:sham-operated group,model group,Benazepril group,low,medium and high-dose groups of SSR.The rats were given the cor-responding intervention for six weeks,then were sacrificed.Serum was examined by enzyme linked immunosorbent assay(ELISA).Cardiac ultrasound was used to detect cardiac function in 5/6 nephrectomized rats.Myocardial tissue was examined by light and electron microscopy;PINK1,Parkin,microtubule-associated protein1 light chain 3 Ⅱ(LC3B),sequestosome 1(P62),BECN1(Beclin-1)and dynamin-related protein 1(Drp-1)were measured by real time polymerase chain reaction(RT-PCR),Western blot(WB)and immunohistochemistry(IHC).RESULTS:The expression levels of blood urea nitrogen(BUN)and creatinine(SCr)in the model group were significantly higher than those in the sham-operated group,indicating that modeling was successful.SSR can protect myocardium by reducing the relative expression of creatine kinase myocardial isoenzyme and hypersensitivity cardiac troponin I(P＜0.05).SSR can improve cardiac function in rats after ultrasound testing.SSR can improve the pathological manifestations of myocardial tissue after Masson staining.SSR can increase the number of autophagosomes and autophagiclysosomes in 5/6 nephrectomized rats(P＜0.05).Determined by RT-PCR,WB and IHC,SSR can increase the relative expression of PINK1,Parkin,and LC3B(P＜0.05),and decrease the relative expression of P62,Beclin-1 and Drp-1(P＜0.05).CONCLUSIONS:The PINK1/Parkin mitochondrial autophagy pathway in myocardial tissues in 5/6 nephrectomy CKD myocardial injury rats was inhibited.SSR can activate PINK1/Parkin mitochondrial autophagy to enhance mitochondrial autophagy,and play a protective role in myocardial tissues.
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