【目的】探讨白芍总苷(the total glucosides of paeony,TGP)对腹膜纤维化大鼠转化生长因子-β1(TGF-β1)的影响。【方法】选用健康SD雄性大鼠32只,随机分为4组,每组8只,分别为空白组、模型组、白芍总苷高剂量组、白芍总苷低剂量组。采...【目的】探讨白芍总苷(the total glucosides of paeony,TGP)对腹膜纤维化大鼠转化生长因子-β1(TGF-β1)的影响。【方法】选用健康SD雄性大鼠32只,随机分为4组,每组8只,分别为空白组、模型组、白芍总苷高剂量组、白芍总苷低剂量组。采用腹腔注射42.5 g/L含糖透析液+脂多糖法复制腹膜纤维化模型。白芍总苷高、低剂量组造模同时给予白芍总苷灌胃(剂量分别为200、100 mg.kg-1.d-1);实验第30天结束后留取腹膜组织和腹透液,采用一步法Real-time PCR测定腹膜组织TGF-β1 mRNA的表达,采用酶联免疫吸附(ELISA)法测定腹透液中TGF-β1的水平。【结果】模型组腹膜TGF-β1mRNA的表达及腹膜透析液TGF-β1的水平显著高于空白组(P<0.001),白芍总苷高、低剂量组2指标水平较模型组均显著降低(P<0.05)。【结论】白芍总苷可以上调TGF-β1的表达,对腹膜纤维化具有一定防治作用。展开更多
Background Transforming growth factor-β1 （TGF-β1） is known to be a key fibrogenic cytokine in a number of chronic fibrotic diseases, including chronic allograft nephropathy. We examined the effects of inhibition o...Background Transforming growth factor-β1 （TGF-β1） is known to be a key fibrogenic cytokine in a number of chronic fibrotic diseases, including chronic allograft nephropathy. We examined the effects of inhibition of TGF-β1 expression by RNA interference on renal allograft fibrosis, and explored the mechanisms responsible for these effects. Methods A Sprague-Dawley-to-Wistar rat model of accelerated kidney transplant fibrosis was used. Sixty recipient adult Wistar rats were randomly divided into four groups： group J （sham-operated group）, group T （plasmid-transfected group）, group H （control plasmid group）, and group Y （transplant only group）. Rats in group T were transfected with 200 μg of TGF-β1 short hairpin RNA （shRNA）. Reverse transcription-polymerase chain reaction and Western blotting were used to examine the expression of TGF-β1, Smad3/7, E-cadherin, and type I collagen. The distribution of type I collagen was measured by immunohistochemistry. The pathologic changes and extent of fibrosis were assessed by hematoxylin and eosin and Masson staining. E-cadherin and α-smooth muscle actin immunohistochemical staining were used to label tubular epithelial cells and fibroblasts, respectively.Results Plasmid transfection significantly inhibited the expression of TGF-β1, as well as that of its target gene, type I collagen （P 〈0.05 and P 〈0.01, respectively）. In addition, the degree of fibrosis was mild, and its development was delayed in plasmid-transfected rats. In contrast, TGF-β1-shRNA transfection maintained the expression of E-cadherin in tubular epithelial cells while it inhibited the transformation from epithelial cells to fibroblasts. Blood urea nitrogen and serum creatinine were lower in the plasmid group than in the control groups （P 〈0.05 and P 〈0.01, respectively）. Conclusions This study suggests that transfection of a TGF-pl-shRNA plasmid could inhibit the fibrosis of renal allografts. The mechanism may be associated with the downregulation of Smad3 and upregulation of Smad7, resulting in suppressed epithelial-myofibroblast transdifferentiation and extracellular matrix synthesis.展开更多
AIM To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model.METHODS ...AIM To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model.METHODS At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments.RESULTS Compared to the wild-type cohort, the PCK kidney(Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort.CONCLUSION These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.展开更多
文摘【目的】探讨补肾活血化痰法改善自发性高血压大鼠(SHR)左心室纤维化机制。【方法】选用20只自发性高血压大鼠,随机分为模型组和中药组,10只WKY大鼠(Wistar-Kyoto rat)作为正常对照组。干预12周后,应用Masson染色法检测大鼠左心室纤维化程度,逆转录—聚合酶链反应(RT-PCR)法检测大鼠左心室Smad3 m RNA表达水平,Western blot法检测大鼠左心室Smad3表达水平。【结果】中药组大鼠心肌纤维化水平、Smad3蛋白表达水平、Smad3基因表达水平显著低于模型组(均P<0.05)。【结论】补肾活血化痰法可能通过抑制Smad3表达改善自发性高血压大鼠左心室纤维化进程。
文摘【目的】探讨白芍总苷(the total glucosides of paeony,TGP)对腹膜纤维化大鼠转化生长因子-β1(TGF-β1)的影响。【方法】选用健康SD雄性大鼠32只,随机分为4组,每组8只,分别为空白组、模型组、白芍总苷高剂量组、白芍总苷低剂量组。采用腹腔注射42.5 g/L含糖透析液+脂多糖法复制腹膜纤维化模型。白芍总苷高、低剂量组造模同时给予白芍总苷灌胃(剂量分别为200、100 mg.kg-1.d-1);实验第30天结束后留取腹膜组织和腹透液,采用一步法Real-time PCR测定腹膜组织TGF-β1 mRNA的表达,采用酶联免疫吸附(ELISA)法测定腹透液中TGF-β1的水平。【结果】模型组腹膜TGF-β1mRNA的表达及腹膜透析液TGF-β1的水平显著高于空白组(P<0.001),白芍总苷高、低剂量组2指标水平较模型组均显著降低(P<0.05)。【结论】白芍总苷可以上调TGF-β1的表达,对腹膜纤维化具有一定防治作用。
文摘Background Transforming growth factor-β1 （TGF-β1） is known to be a key fibrogenic cytokine in a number of chronic fibrotic diseases, including chronic allograft nephropathy. We examined the effects of inhibition of TGF-β1 expression by RNA interference on renal allograft fibrosis, and explored the mechanisms responsible for these effects. Methods A Sprague-Dawley-to-Wistar rat model of accelerated kidney transplant fibrosis was used. Sixty recipient adult Wistar rats were randomly divided into four groups： group J （sham-operated group）, group T （plasmid-transfected group）, group H （control plasmid group）, and group Y （transplant only group）. Rats in group T were transfected with 200 μg of TGF-β1 short hairpin RNA （shRNA）. Reverse transcription-polymerase chain reaction and Western blotting were used to examine the expression of TGF-β1, Smad3/7, E-cadherin, and type I collagen. The distribution of type I collagen was measured by immunohistochemistry. The pathologic changes and extent of fibrosis were assessed by hematoxylin and eosin and Masson staining. E-cadherin and α-smooth muscle actin immunohistochemical staining were used to label tubular epithelial cells and fibroblasts, respectively.Results Plasmid transfection significantly inhibited the expression of TGF-β1, as well as that of its target gene, type I collagen （P 〈0.05 and P 〈0.01, respectively）. In addition, the degree of fibrosis was mild, and its development was delayed in plasmid-transfected rats. In contrast, TGF-β1-shRNA transfection maintained the expression of E-cadherin in tubular epithelial cells while it inhibited the transformation from epithelial cells to fibroblasts. Blood urea nitrogen and serum creatinine were lower in the plasmid group than in the control groups （P 〈0.05 and P 〈0.01, respectively）. Conclusions This study suggests that transfection of a TGF-pl-shRNA plasmid could inhibit the fibrosis of renal allografts. The mechanism may be associated with the downregulation of Smad3 and upregulation of Smad7, resulting in suppressed epithelial-myofibroblast transdifferentiation and extracellular matrix synthesis.
文摘AIM To evaluate the novel platelet-derived growth factor receptor and vascular endothelial growth factor receptor dual kinase inhibitor ANG3070 in a polycystic kidney disease-congenital hepatic fibrosis model.METHODS At 6 wk of age, PCK rats were randomized to vehicle or ANG3070 for 4 wk. At 10 wk, 24 h urine and left kidneys were collected and rats were continued on treatment for 4 wk. At 14 wk, 24 h urine was collected, rats were sacrificed, and liver and right kidneys were collected for histological evaluation. For Western blot studies, PCK rats were treated with vehicle or ANG3070 for 7 d and sacrificed approximately 30 min after the last treatments.RESULTS Compared to the wild-type cohort, the PCK kidney(Vehicle cohort) exhibited a marked increase in kidney and liver mass, hepato-renal cystic volume, hepato-renal fibrosis and hepato-renal injury biomarkers. Intervention with ANG3070 in PCK rats decreased kidney weight, reduced renal cystic volume and reduced total kidney hydroxyproline, indicating significantly reduced rental interstitial fibrosis compared to the PCK-Vehicle cohort. ANG3070 treatment also mitigated several markers of kidney injury, including urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, cystatin C and interleukin-18 levels. In addition, this treatment attenuated key indices of renal dysfunction, including proteinuria, albuminuria and serum blood urea nitrogen and creatinine, and significantly improved renal function compared to the PCK-Vehicle cohort. ANG3070 treatment also significantly decreased liver enlargement, hepatic lesions, and liver fibrosis, and mitigated liver dysfunction compared to the PCK-Vehicle cohort.CONCLUSION These results suggest that ANG3070 has the potential to slow disease, and may serve as a bridge toward hepato-renal transplantation in patients with fibropolycystic disease.
