OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it ...OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it reduces of renal fibrosis.METHODS:Male Wistar rats were randomly divided into 4 groups:the sham group,UUO group(180 d of left ureter ligation),UUO plus eplerenone(EPL)group,and UUO plus HJHR group.After 180 d of oral drug administration,blood and contralateral kidneys were collected for analysis.Angiogenesis-and fibrosis-related indexes were detected.RESULTS:HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels ofα-smooth muscle actin(α-SMA),vimentin and collagen I.Moreover,these treatments could reduce the expression of vascular endothelial growth factor-A(VEGFA)by inhibiting the infiltration of macrophages.Furthermore,HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production,which inhibited angiogenesis.Finally,the coexpressions of CD34,CD105 andα-SMA were decreased in the HJHR and EPL groups,indicating that endothelial-to-mesenchymal transition was inhibited.CONCLUSIONS:These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFAinduced angiogenesis,encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.展开更多
Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress of renal fibrosis. Peroxisome proliferator-activated receptor-γ（PPARγ） agon...Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress of renal fibrosis. Peroxisome proliferator-activated receptor-γ（PPARγ） agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction（UUO） was used to establish a different renal fibrosis model. PPARγ agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14 th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for α-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4＋ T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.展开更多
Objective:To study the changes of the expression of bone morphogenetic protein-7(BMP-7) and its receptors(BMPR-Ⅱ,ALK2,ALK3 and ALK6) in the renal tubulointerstitial fibrosis induced with unilateral ureteral obstructi...Objective:To study the changes of the expression of bone morphogenetic protein-7(BMP-7) and its receptors(BMPR-Ⅱ,ALK2,ALK3 and ALK6) in the renal tubulointerstitial fibrosis induced with unilateral ureteral obstruction in rats. Methods: Sixty Wistar male rats were divided randomly into the normal control,sham-operation and unilateral ureteral obstruction(UUO) groups and the rats were killed on the 1st,3rd,7th and 14th postoperative days respectively.The mRNA level of BMP-7,BMPR-Ⅱ,ALK2,ALK3 and ALK6 was determined with RT-PCR.The site and level of protein expression of BMP-7 were observed with immunohistochemical staining. Results: The mRNA level of BMP-7,BMPR-Ⅱ,ALK2 and ALK3 was significantly decreased in the rats of UUO group than in those of the sham-operation group but the mRNA level of ALK6 showed no obvious changes in all the rats.Immunohistochemical staining revealed that the protein of BMP-7 was mainly expressed in the renal tubules and interstitial tissue of the kidneys in normal rats but it was decreased gradually along with the unilateral ureteral obstruction. Conclusion: It is found that the loss of BMP-7 and its receptors including BMPR-Ⅱ,ALK2 and ALK3 occurs in the early phase of renal tubulointerstitial fibrosis before the appearance of other pathological changes in the kidney and may play an important role in the occurrence and progress of renal tubulointerstitial fibrosis.展开更多
Objective: To explore the role of bone morphorgenetic protein-7 （BMP-7） in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods: Sixty Wistar rats were equally and random...Objective: To explore the role of bone morphorgenetic protein-7 （BMP-7） in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods: Sixty Wistar rats were equally and randomly divided into normal control, sham operation and UUO groups, and respectively sacrificed on the 1st, 3rd, 7th, 14th day after the time of UUO operation. The mRNA levels of BMP-7 and TGF-β1 in the renal tissues were examined by RT-PCR. The expression sites and levels of BMP-7 and TGF-β1 proteins were detected by immunohistochemistry staining. Results:Compared to control groups, the level of BMP-7 mRNA was significantly decreased, but that of TGF-β1 mRNA was significantly increased in UUO rats. Immunohistochemistry staining indicated that BMP-7 mainly expressed in the renal tubules and interstitum, rarely in the glomeruli. In UUO rats, the expression of BMP-7 protein was decreased, but that of TGF-β1 was increased in an obstruction dependent manner. Conclusion:The down- regulation of BMP-7 is observed in the early phase of fibrotic process of the renal interstitium, suggesting it may be involved in the formation and development of the tubulo-interstitial lesions.展开更多
【Objective】To explore the effect of unilateral ureteral obstruction on the adrenal function in a rat model.【Methods】36 SD rats were randomly divided into two groups:unilateral ureteral obstruction(UUO)model was em...【Objective】To explore the effect of unilateral ureteral obstruction on the adrenal function in a rat model.【Methods】36 SD rats were randomly divided into two groups:unilateral ureteral obstruction(UUO)model was employed,and sham-operated rats were used as control.28 days after surgery,all the rats were submitted to maximum exercise tolerance test(METT),and the maximum aerobic velocity was observed.At the day 0,day 28,and after METT,the serum levels of adrenaline,noradrenaline and corticosterone in rats were detected by ELISA.【Results】1 The maximum aerobic velocity in UUO model rats was lower than that in control rats(P<0.05).2 At the beginning(day 0),there no significant difference were found in the levels of adrenaline,noradrenaline and corticosterone between two groups.3 28 days after surgery,the levels of adrenaline,noradrenaline and corticosterone in UUO model rats were slightly higher than those in control rats,but the differences were not significant(P>0.05).4After METT,the levels of adrenaline and corticosterone in UUO model rats were lower than those in control rats significantly(P<0.05).The level of noradrenaline in UUO model rats was higher than that in control rats,but there is no significant difference between two groups(P>0.05).【Conclusions】Unilateral ureteral obstruction resulted in the decrease of exercise tolerance in rats,which may contribute to the inhibition of the adrenal secretion.展开更多
基金Natural Science Foundation-funded Project:Effect of Macrophage-to-Myofibroblast Transition in Contralateral Kidney of Unilateral Ureteral Obstruction Rats Through the Aldosterone/MR/SGK1 Pathway and Inhibition of Chinese Herbs(No.81873251)Natural Science Foundation-funded Project:Aldosterone Stimulates MR Activation to Induce Lymphangiogenesis in the Contralateral Kidney of UUO Rats and the Protective Effect of Yiqi Jiedu Huayu Herbs(No.82174317)+1 种基金Hebei Provincial Postgraduate Innovative Ability Cultivation Funding Project:Aldosterone Induced Macrophages to Secrete VEGFA to Participate in Renal Angiogenesis and the Protective Effect of Huoxue Jiedu Huayu Recipe(CXZZBS2023140)Construction Program of New Research and Development Platform and Institution,Hebei Province Innovation Ability Promotion Plan under Grant No.20567624H。
文摘OBJECTIVE:To elucidate the mechanism by which Huoxue Jiedu Huayu recipe(活血解毒化瘀方,HJHR)regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction(UUO)rats and the mechanism by which it reduces of renal fibrosis.METHODS:Male Wistar rats were randomly divided into 4 groups:the sham group,UUO group(180 d of left ureter ligation),UUO plus eplerenone(EPL)group,and UUO plus HJHR group.After 180 d of oral drug administration,blood and contralateral kidneys were collected for analysis.Angiogenesis-and fibrosis-related indexes were detected.RESULTS:HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels ofα-smooth muscle actin(α-SMA),vimentin and collagen I.Moreover,these treatments could reduce the expression of vascular endothelial growth factor-A(VEGFA)by inhibiting the infiltration of macrophages.Furthermore,HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production,which inhibited angiogenesis.Finally,the coexpressions of CD34,CD105 andα-SMA were decreased in the HJHR and EPL groups,indicating that endothelial-to-mesenchymal transition was inhibited.CONCLUSIONS:These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFAinduced angiogenesis,encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.
基金financially supported by grants from the National Natural Science Foundation of China(No.81470948,No.81270770,and No.81300575)Hubei Provincial Health and Family Planning Youth Project of China(No.WJ2015Q007)
文摘Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress of renal fibrosis. Peroxisome proliferator-activated receptor-γ（PPARγ） agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction（UUO） was used to establish a different renal fibrosis model. PPARγ agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14 th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for α-SMA, and Western blotting for α-SMA and PDGFR-β, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF-β and MCP-1 had no significant changes, at the same time, CD4＋ T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO.
文摘Objective:To study the changes of the expression of bone morphogenetic protein-7(BMP-7) and its receptors(BMPR-Ⅱ,ALK2,ALK3 and ALK6) in the renal tubulointerstitial fibrosis induced with unilateral ureteral obstruction in rats. Methods: Sixty Wistar male rats were divided randomly into the normal control,sham-operation and unilateral ureteral obstruction(UUO) groups and the rats were killed on the 1st,3rd,7th and 14th postoperative days respectively.The mRNA level of BMP-7,BMPR-Ⅱ,ALK2,ALK3 and ALK6 was determined with RT-PCR.The site and level of protein expression of BMP-7 were observed with immunohistochemical staining. Results: The mRNA level of BMP-7,BMPR-Ⅱ,ALK2 and ALK3 was significantly decreased in the rats of UUO group than in those of the sham-operation group but the mRNA level of ALK6 showed no obvious changes in all the rats.Immunohistochemical staining revealed that the protein of BMP-7 was mainly expressed in the renal tubules and interstitial tissue of the kidneys in normal rats but it was decreased gradually along with the unilateral ureteral obstruction. Conclusion: It is found that the loss of BMP-7 and its receptors including BMPR-Ⅱ,ALK2 and ALK3 occurs in the early phase of renal tubulointerstitial fibrosis before the appearance of other pathological changes in the kidney and may play an important role in the occurrence and progress of renal tubulointerstitial fibrosis.
文摘Objective: To explore the role of bone morphorgenetic protein-7 （BMP-7） in the renal tubulo-interstitial lesions induced by unilateral ureteral obstruction （UUO）. Methods: Sixty Wistar rats were equally and randomly divided into normal control, sham operation and UUO groups, and respectively sacrificed on the 1st, 3rd, 7th, 14th day after the time of UUO operation. The mRNA levels of BMP-7 and TGF-β1 in the renal tissues were examined by RT-PCR. The expression sites and levels of BMP-7 and TGF-β1 proteins were detected by immunohistochemistry staining. Results:Compared to control groups, the level of BMP-7 mRNA was significantly decreased, but that of TGF-β1 mRNA was significantly increased in UUO rats. Immunohistochemistry staining indicated that BMP-7 mainly expressed in the renal tubules and interstitum, rarely in the glomeruli. In UUO rats, the expression of BMP-7 protein was decreased, but that of TGF-β1 was increased in an obstruction dependent manner. Conclusion:The down- regulation of BMP-7 is observed in the early phase of fibrotic process of the renal interstitium, suggesting it may be involved in the formation and development of the tubulo-interstitial lesions.
基金supported by National Natural Science Foundation of China(No.30801505)
文摘【Objective】To explore the effect of unilateral ureteral obstruction on the adrenal function in a rat model.【Methods】36 SD rats were randomly divided into two groups:unilateral ureteral obstruction(UUO)model was employed,and sham-operated rats were used as control.28 days after surgery,all the rats were submitted to maximum exercise tolerance test(METT),and the maximum aerobic velocity was observed.At the day 0,day 28,and after METT,the serum levels of adrenaline,noradrenaline and corticosterone in rats were detected by ELISA.【Results】1 The maximum aerobic velocity in UUO model rats was lower than that in control rats(P<0.05).2 At the beginning(day 0),there no significant difference were found in the levels of adrenaline,noradrenaline and corticosterone between two groups.3 28 days after surgery,the levels of adrenaline,noradrenaline and corticosterone in UUO model rats were slightly higher than those in control rats,but the differences were not significant(P>0.05).4After METT,the levels of adrenaline and corticosterone in UUO model rats were lower than those in control rats significantly(P<0.05).The level of noradrenaline in UUO model rats was higher than that in control rats,but there is no significant difference between two groups(P>0.05).【Conclusions】Unilateral ureteral obstruction resulted in the decrease of exercise tolerance in rats,which may contribute to the inhibition of the adrenal secretion.
