Interventional effect of epalrestat on renal interstitial fibrosis in unilateral ureteral obstruction rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To observe the protective effects of epalrestat (EPS) on interstitial fibrosis in unilateral ureteral obstruction (UUO) rats and its mechanism.@*METHODS@#Rats were randomly divided into four groups: sham group, UUO group, UUO + epalrestat (50 or 100 mg/kg), 8 rats in each group.Rats in UUO and UUO + epalrestat group were obstructed left ureter.In the sham group, rats had their left ureters exposed and manipulated without ligation.Animals for epalrestat treatment received daily drug via gavage for 3 weeks, the rats of sham and UUO groups received equal amount of sodium carboxymethyl cellulose with the same regimen.Renal tissues pathological changes and collagen deposition were observed by HE and Masson's staining.The aldose reductase(AR) expression in renal tissues was measured by immunohistochemisty.The expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), fibroblast-specific protein1 (FSP-1), fibronectin (FN), epithelial cadherin (E-cadherin), transforming growth factor-β1 (TGF-β1) and AR from kidney tissues were measured by real-time RT-PCR or Western blot.@*RESULTS@#Compared with the sham group, the renal tissues of the UUO group showed significant fibrosis, including renal tubular epithelial cell atrophy and vacuolated degeneration, collagen deposition, fibroblasts and myofibroblasts proliferation and inflammatory cell infiltration, and concomitantly with the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably up-regulated, but E-cadherin was significantly reduced in UUO group.Compared with the UUO group, after 3 weeks epalrestat administration, the level of renal interstitial fibrosis was obviously ameliorated and the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably down-regulated, but E-cadherin was significantly increased in rats of epalrestat groups.@*CONCLUSION@#These results suggest that epalrestat attenuates renal interstitial fibrosis possibly through inhibition of EMT via inhibiting TGF-β1 and AR expression.

Rutaecarpine protects against bleomycin-induced pulmonary fibrosis through inhibiting Notch1/eIF3a signaling pathway in rats / 中国中药杂志

To investigate whether the protection of rutaecarpine against bleomycin-induced pulmonary fibrosis is mediated by inhibiting Notch1/eukaryotic initiation factor 3a (eIF3a) signaling pathway, and whether these effects are related to the synthesis and release of calcitonin gene-related peptide (CGRP) and inhibition of epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, male Sprague-Dawley rats were randomly divided into five groups (=12), respectively, Control group, bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group and capsaicin plus rutaecarpine (300 mg·kg⁻¹) group. Bleomycin (5 mg·kg⁻¹) was used to induce pulmonary fibrosis rat model. Rats were given capsaicin (50 mg·kg⁻¹) by subcutaneous injections 1 days before and 7, 14, 21 days after induce pulmonary fibrosis rat model to deplete endogenous CGRP. At the end of experiments, blood was collected from carotid artery to determinate the plasma levels of CGRP by ELISA. Pulmonary tissue change was observed by HE staining. Masson's trichrome stain was used to demonstration collagen deposition. The collagen I expression in pulmonary tissue was measured by immunohistochemisty. The expression of CGRP, Notch1, eIF3a, collagen I, vimentin, alpha-smooth muscle actin (α-SMA), E-cadherin and zonula occludens-1 (ZO-1) was detected by qPCR or Western blot. Compared with the control group, the pulmonary tissue of the bleomycin group showed significant fibrosis, including significant disturbed alveolar structure, marked thickening of the interalveolar septa and dense interstitial infiltration by inflammatory cells and fibroblasts, and concomitantly with the decrease in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was decreased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was increased in bleomycin group (<0.05 or <0.01). Compared with the bleomycin group, rutaecarpine (100, 300 mg·kg⁻¹) group significantly reduced bleomycin-induced pulmonary injury concomitantly with the increase in plasma CGRP and expression of CGRP. Importantly the expression of E-cadherin and ZO-1 was increased and expression of Notch1, eIF3a, collagen I, vimentin and α-SMA was decreased by rutaecarpine treatment (<0.05 or <0.01). All these effects of rutaecarpine were abolished by capsaicin.These results suggest that rutaecarpine protects against bleomycin-induced pulmonary fibrosis by inhibiting Notch1/eIF3a signaling pathway, alleviating EMT process, which is related to the increased synthesis and release of CGRP.

Effect of sesamin on pulmonary vascular remodeling in rats with monocrotaline-induced pulmonary hypertension / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH).</p><p><b>METHOD</b>Totally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot.</p><p><b>RESULT</b>After the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC.</p><p><b>CONCLUSION</b>Sesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury.</p>