化浊解毒方调控线粒体动力学保护慢性肾衰竭大鼠肾功能的作用研究OA

Objective To study the mechanism of Huazhuo Jiedu Decoction protecting renal function in rats with chronic renal failure(CRF)by regulating renal mitochondrial dynamics.Methods The rat model of chronic renal failure(CRF)was established by 5/6 nephrectomy.11 of 67 SD rats were randomly selected as the sham operation group and 56 as the model group,and the successfully modeled SD rats were divided into the model group,the Huazhuo Jiedu Decoction low-dose group(1.175 g/kg),the Huazhuo Jiedu Decoction medium-dose group(2.35 g/kg),the Huazhuo Jiedu Decoction high-dose group(4.7 g/kg),the losartan potassium group(4.5×10-3 g/kg),9 rats in each group.The administration groups were given the corresponding drugs by gavage,and the sham operation group and the model group were given the same amount of normal saline for 8 weeks.The pathological changes of renal tissue were observed by hematoxylin-eosin(HE)staining and Masson's trichrome stain(Masson)staining.The ultra-structural changes of mitochondria in renal tubular epithelial cells were observed by transmission electron microscopy.The expression levels of dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),mitochondrial fusion protein 2(Mfn2),Bcl-2-related X protein(Bax)and B-cell lymphoma-2(Bcl-2)were detected by western blot(WB).The expression levels of Drp1 and Mfn2 proteins were detected by immunohistochemistry.The levels of adenosine triphosphate(ATP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)in kidney were detected by colorimetry.Results Compared with the sham operation group,some glomeruli atrophy,mesangial cells and matrix hyperplasia,structural disorder of renal tubulointerstitial area,tubular brush border shedding,vacuolar degeneration,partial renal tubular atrophy,and a large number of blue collagen fibers accumulated in periglomerular and interstitial tissues were showed in the model group.Renal tubular epithelial cells mitochondrial swelling,ridge fracture,vacuolar degeneration.The expression levels of Drp1 and Bax protein were significantly increased(P<0.01),and the expression levels of Mfn1、Mfn2 and Bcl-2 protein were significantly decreased(P<0.05,P<0.01).The contents of ATP,ADP and AMP were significantly decreased(P<0.01).After the intervention of Huazhuo Jiedu Decoction,the above pathological damage was significantly improved,mi-tochondrial structure damage of renal tubular epithelial cells was reduced.The expression levels of Drp1 and Bax protein were significantly decreased(P<0.05,P<0.01),and the expression levels of Mfn1、Mfn2 and Bcl-2 protein were significantly increased(P<0.05,P<0.01).The values of ATP,ADP and AMP were significantly increased(P<0.05,P<0.01).Conclusion Huazhuo Jiedu Decoction can effectively improve the renal function of 5/6 nephrectomy rats.This renal protective effect may be related to the reduction of Drp1 protein level and the increase of Mfn1、Mfn2 protein expression level,thereby improving mitochondrial dynamics,increasing ATP production,inhibiting apoptosis and reducing renal fibrosis.