Effect of a novel phosphodiesterase type 5 inhibitor,CPD1,on unilateral renal interstitial fibrosis caused by ureteric obstruction in mice / 中国药理学通报

Aim To investigate the effects of CPD1,a novel phosphodiesterase 5 inhibitor,on renal pathological phenotype and fibrotic protein expression in renal fibrosis model mice. Methods Male C57BL/6 J mice were divided into three groups randomly(sham group,UUO group and UUO+CPD1 group). Unilateral ureteric obstruction model was constructed by surgery,and CPD1(5 mg·kg-1·d-1)was administered by intragastric administration two hours after the modeling for seven days. HE and Sirius Red staining were used to observe the distribution of tissue structural lesions and fibrosis. Immunohistochemical staining and Western blot were used to detect the expression of fibronectin(FN),α-SMA,collagen-I and kidney injury molecule-1(Kim-1). Results Compared with sham operation group,the renal tubules of mice were dilated and accompanied by a large amount of inflammatory infiltration. Moreover,the expressions of FN,α-SMA,collagen-I and Kim-1 proteins increased significantly(P<0.05)in UUO group. CPD1 treatment improved the kidney structure and decreased the expression of collagen fibers. Furthermore,CPD1 inhibited the expression of FN,α-SMA,collagen-I and Kim-1 markedly(P<0.05). Conclusions Phosphodiesterase 5 inhibitor CPD1 alleviates the progression of renal fibrosis induced by unilateral ureteral obstruction through down-regulating ECM deposition in the extracellular matrix and expression of Kim-1. The specific mechanism remains to be further studied.

Differentially expressed gene screening of urinesamples from rats renal fibrosis model and bioinformatics analysis / 基础医学与临床

Objective To investigate the differentially expressed genes of urine samples from renal fibrosis model and carry out bioinformatics analysis.Methods Rat renal fibrosis model was constructed with the method of unilateral ureteric obstruction.Urine were collected from the rats with unilateral obstructive nephropathy and sham group, respectively.Total RNA was extracted and sequencing library was established.Differential expression mRNA were analyzed by GO and KEGG pathway.Known pre-miRNA were detected and novel lncRNA family were classified.Results Compared with the sham group urine, 813 up-regulated mRNA/lncRNA and 213 down-regulated mRNA/lncRNA were collected from the urine of renal fibrosis rats.Conclusions There are significant differential expression profile in urine samples between renal fibrosis rat group and the shame group.With high-throughput transcriptome sequencing and bioinformatics analysis, the exciting possibility was raised for better understanding renal pathologies and development of new diagnostic biomarkers.