Intervention Of Curcumin On Renal Injury Induced By Aristolochic Acid Ⅰ In Rats Study On Function And Mechanism

Aristolochic acid Ⅰ(AA-I)is a kind of active ingredient commonly found in Aristolochic plants,and has many biological functions such as antipyretic,analgesic,anti-inflammatory and expectorant.However,long-term low-dose or short-term high-dose exposure to AA-I drugs can cause kidney injury and pose a potential threat to animal health and animal-derived food.Curcumin(CUR)is a polyphenolic active ingredient extracted from rhizomes of Zingiberaceae and Arisaemataceae plants,which has biological effects such as anti-tumor,anti-apoptosis,anti-oxidation and lipid-lowering.In order to study the intervention effect and mechanism of curcumin on renal injury in rats exposed to aristolochic acid I,36 SD rats with an average weight of 200±10g were randomly divided into four groups : control group(Control),aristolochic acid I group(AA),curcumin group(CUR)and curcumin intervention group(AA+CUR).Control group rats were given polyethylene glycol 400(PEG400)and saline solution by gavage;The AA group was intragastrically administered with PEG400 and normal saline mixture,and then intragastrically administered with 10 mg/kg AA-I after 2h;The CUR group was intragastrically administered with PEG400 and normal saline mixture,and 200mg/kg CUR was intragastrically administered 2h later.AA + CUR group was given 10mg/kg AA-I by gavage,and 200mg/kg CUR by gavage after 2h.The experiment lasted four weeks.The blood and kidney of rats in each group were collected.The renal function damage was detected by BUN and Cr kits,and the pathological changes of renal structure were observed by H.E.staining.MDA,GSH,GST and SOD kits were used to detect renal oxidative stress;ATP content kit was used to detect the damage degree of renal mitochondria;TUNEL staining kit was used to detect the apoptosis of renal tubular epithelial cells;Immunohistochemical staining was used to detect the expression of SIRT1 and Nrf2 proteins in rat kidney;The m RNA and protein expressions of SIRT1,Nrf2,HO-1,NQO1,Keap1,Caspase-3,Caspase-9,Bax and Bcl-2 were detected by q RT-PCR and Western blot.The aim was to evaluate the intervention effect and mechanism of CUR on renal injury in AA-I exposed rats.Results:(1)AA-I treatment can cause renal injury.AA-I treatment can increase BUN and Cr content and lead to swelling of renal tubular epithelial cells,vacuolar degeneration,a small number of renal tubular epithelial cells shedding,nuclear loss,cell shrinkage,inflammatory cell infiltration in renal interstitial and luminal stenosis.CUR intervention can improve the damage of renal structure and function caused by AA-I;(2)AA-I treatment increased the content of MDA and decreased the activities of SOD,GST and GSH in kidney of rats.CUR intervention could alleviate oxidative stress injury;(3)AA-I treatment could down-regulate the expression of SIRT1,Nrf2,Keap1,NQO1 and HO-1 genes and proteins in rat kidney,and CUR intervention could up-regulate the expression of the above genes and proteins;(4)AA-I treatment could induce the damage of kidney mitochondria in rats,resulting in the decrease of ATP content.CUR could increase the ATP content of damaged kidney tissue and reduce the apoptosis rate caused by mitochondrial apoptosis pathway;(5)AA-I treatment could increase the positive rate of renal apoptotic cells in rats,reduce the expression of Bcl-2 protein and gene,and increase the expression of Bax,Caspase-9 and Caspase-3 protein and gene to aggravate apoptosis.CUR intervention could alleviate AA-I-induced apoptosis by inhibiting the activation of Bax,Caspase-9 and Caspase-3 and increasing the activation of Bcl-2.Conclusion: CUR can effectively alleviate renal oxidative stress and apoptosis caused by AA-I by activating SIRT1/Nrf2/HO-1 signaling pathway,thereby alleviating renal injury caused by AA-I.