Objective To observe the effects of different ligation sites and fasting method on a C57BL/6J mouse model of partial bile duct ligation(pBDL)-induced cholestasis,to establish a pBDL modeling method with a high modeling rate,typical symptoms,and good stability.Methods C57BL/6J mice were subjected to selective ligation of the left hepatic bile duct(L-pBDL)and left-to-median bile duct junction ligation(ML-pBDL)for modeling,and the effects of different pBDL ligation method on serum alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase(ALP),total bilirubin,total bile acid,and liver histopathology were observed.The effects of different fasting method on symptoms and liver injury in the ML-pBDL model were also observed after fasting for 12 and 16 h before surgery,and for 4 h after surgery.Results(1)The incidence of jaundice in the ML-pBDL group was 52.94%and the survival rate within 3 weeks after surgery was 64.71%,while the incidence of jaundice in the L-pBDL group was 11.76%and the survival rate within 3 weeks after surgery was 82.35%.Compared with those in the sham surgery group,serum liver function indicators were significantly increased in the L-pBDL and ML-pBDL groups(P＜0.01),and ALP activity was significantly higher in the ML-pBDL group than in the L-pBDL group(P＜0.05).Compared with mice in the L-pBDL group,mice in the ML-pBDL group had more severe liver fibrosis at 3 weeks post-surgery(P＜0.01).(2)In addition,the incidence of jaundice in the 16 h fasting group was 93.33%and the survival rate within 3 weeks after surgery was 73.77%,while the incidence of jaundice in the 12 h fasting group was 42.86%and the survival rate within 3 weeks after surgery was 71.42%.Compared with those in the normal group,ALP activity,alanine aminotransferase/aspartate aminotransferase ratio,total bile acid level,and proportion of collagen fiber area were all significantly increased in the 16 h and 12 h fasting groups(P＜0.05).Although the observed indicators were higher in the 16 h fasting group compared with those in the 12 h fasting group,the difference was not significant(P＞0.05).Mice in the 12 h and 16 h fasting groups both showed significant bile duct hyperplasia and liver fibrosis(P＜0.01),with more severe liver fibrosis in the 16 h fasting group(P＜0.01).Conclusions Both L-pBDL and ML-pBDL ligation method can be used to establish a mouse model of cholestasis;however,symptoms in the L-pBDL model only exhibit transient damage characteristics,while the liver lesions in the ML-pBDL model are typical and stable.Prolonging the preoperative fasting time can improve the modeling rate and stability of the ML-pBDL model and produce more-typical pathological symptoms.

Uric acid (UA), the final product of human purine metabolism, can cause hyperuricemia (HUA) when excessively accumulated. HUA is closely linked to chronic kidney diseases (CKD) and is considered an independent risk factor. Hyperuricemic nephropathy, a form of CKD induced by HUA, has seen significant advances in understanding through research into the pathogenic roles of uric acid and the development of HUA animal models. Although progress has been made in understanding the pathophysiological mechanisms by which UA induces CKD, much remains to be learned about its pathological molecular mechanisms. New approaches in animal modeling or the selection of model animals may potentially lead to significant breakthroughs in research on hyperuricemia as well as related CKD. This paper reviews the research progress on the molecular mechanisms of hyperuricemic nephropathy, focusing on oxidative stress, inflammation, autophagy, fibrosis, and gut microbiota. Oxidative stress is induced by uric acid intracellularly through xanthine oxidase, NADPH oxidases, and mitochondria, leading to cellular damage. In terms of inflammation, uric acid crystals can activate the NLRP3 inflammasome, triggering an inflammatory cascade. The role of free uric acid as a pro-inflammatory agent, however, remains controversial. Depending on the study conducted, autophagy has been found to either alleviate or exacerbate inflammation induced by uric acid. Fibrosis, particularly through epithelial-mesenchymal transition (EMT), is a major mechanism by which uric acid causes glomerulosclerosis and tubulointerstitial fibrosis. Extensive research has explored various signaling pathways involved in uric acid-induced EMT. Beneficial gut microbiota protect the kidneys by synthesizing short-chain fatty acids, reducing urea’s enterohepatic circulation, and decreasing uric acid production. This paper aims to enhance understanding of the complex relationships between HUA and CKD, serving as a reference for further research and new drug development.