Expression Of FRX And Gpbar1 In The Kidney Of Obstructive Jaundice Rats And The Intervention Role Of Chinese Herbs For Clearing Heat And Removing Dampness

Objective:The aim of this study was to investigate the expression of farnesoid X receptor(FXR)and takeda G protein-coupled receptor1(Gpbar1)in the kidney of obstructive jaundice rats.After the intervention of Chinese herbal medicine Qingrelidan Decoction(QRLDT)and Yinchenhao Decoction(YCHT),the relationship between FXR and Gpbar1 protein expression and Chinese medicine were explored.The protective effect of traditional Chinese medicine on kidney injury in OJ rats were studied.This provide a theoretical basis for clinical treatment of OJ induced kidney injury.Method:1.Grouping: 42 healthy adult male Sprague-Dawley rats weighing between 220 g and 260 g were randomly divided into the following six groups: control group(CON);common bile duct ligation group(BDL);S-Adenosylmethionine group(SAM);Qingrelidan Decoction Group(QRLDT);Yinchenhao Decoction Group(YCHT)and Oleanolic acid group(OA),with 7 rats in each group.2.Preparation of model: SD rats in each group were fasted for 12 hours before operation,and they were drunk freely.After 7 days of adaptive feeding,the OJ model was prepared.Preoperative anesthesia,after the rats were unaware,prepare skin and disinfect.The operation was performed by common bile duct ligation.An incision of about 2cm is made in the middle of the abdomen below the xiphoid process,then exposed the abdominal,dissociated and ligated the common bile duct,closed the abdomen and sutured finally.In CON group,only common bile duct was freed.The remaining drug intervention groups were given their respective medications on the first postoperative day for 14 days.Rats in the CON group and the BDL group were given the same amount of normal saline.3.Specimen collection: After 14 days of modeling,rat kidney tissue and serum samples were collected from each group.Half of kidney tissues were fixed in 4%paraformaldehyde solution,and all the remaining samples were stored at-80 °C for later use.4.Indicators detection: 14 days after modeling,The changes of serum alanine urea nitrogen(Urea),creatinine(Cre),uric acid(UA),total bile acid(TBA),total bilirubin(TBIL),direct bilirubin(DBIL),aminotransferase(ALT),aspartate aminotransferase(AST)were tested.The levels of urinary creatinine and urinary bilirubin in each group were measured at 7 and 14 days.The pathological changes of HE staining were observed.Western blot and immunohistochemistry was used to detect FXR,Gpbar1 protein expression levels.The expression of FXR and Gpbar1 m RNA was detected by real-time fluorescence quantitative polymerase chain reaction(q RT-PCR).The total superoxide dismutase(SOD)activity of kidney was detected by NBT method,and the malondialdehyde(MDA)level of kidney was detected by MDA-TBA colorimetry.Result:Compared with the CON group,serum Urea,Cre,UA,TBIL,DBIL,TBA,ALT,and AST levels increased after 14 days in the BDL group(P < 0.05).Compared with the BDL group,Cre,TBA,and ALT were decreased in each drug intervention group(P <0.05).Compared with the CON group,the urinary creatinine(P<0.05)and urinary bilirubin levels were increased in the BDL group.Compared with the BDL group,the urinary creatinine level was lower in each intervention group(P<0.05),the OA group decreased significantly;the urinary bilirubin levels in each intervention group were decreased.Compared with the CON group,the SOD activity in the BDL group was decreased(P < 0.05)and the MDA level was increased(P < 0.05).Compared with the BDL group,SOD activity was increased in each drug intervention group(P < 0.05),and MDA level was decreased(P < 0.05).Compared with the CON group,the expression levels of FXR and Gpbar1 protein in the BDL group were decreased(P < 0.05);compared with the BDL group,the expression levels of FXR and Gpbar1 protein were increased in each drug intervention group(P < 0.05).Compared with the CON group,the m RNA expression levels of FXR and Gpbar1 in the BDL group were significantly decreased(P <0.01);compared with BDL,the expression level of FXR m RNA was increased in each drug intervention group(P <0.05);QRLDT group and YCHT group Gpbar1 m RNA expression levels were increased(P < 0.05).In conclusion:Compared with normal rats,the expression of bile acid receptors FXR and Gpbar1 in kidney of OJ rats was decreased,which may be related to OJ-induced kidney injury.Increasing the expression of FXR and Gpbar1 in the kidney maybe reduce the OJ-induced kidney injury.Administration of QRLDT and YCHT can increase the expression of FXR and Gpbar1 in the kidney of OJ rats.It may protect the OJ-induced renal injury by reducing the oxidative stress reaction of the kidney.Bile acid receptors FXR and Gpbar1 may be potential therapeutic targets for OJ-induced kidney injury in the future.