Shenmai Injection Improves Hypertensive Heart Failure by Inhibiting Myocardial Fibrosis via TGF-β 1/Smad Pathway Regulation / 中国结合医学杂志

OBJECTIVE@#To study effects of Shenmai Injection on hypertensive heart failure and its mechanism for inhibiting myocardial fibrosis.@*METHODS@#Salt-sensitive (Dahl/SS) rats were fed with normal diet (0.3% NaCl) and the high-salt diet (8% NaCl) to observe the changes in blood pressure and heart function, as the control group and the model group. Salt-insensitive rats (SS-13BN) were fed with the high-salt diet (8% NaCl) as the negative control group. After modeling, the model rats were randomly divided into heart failure (HF) group, Shenmai Injection (SMI) group and pirfenidone (PFD) group by a random number table, with 6 rats in each group. They were given sterilized water, SMI and pirfenidone, respectively. Blood pressure, cardiac function, fibrosis and related molecular expression were detected by sphygmomanometer, echocardiogram, enzyme linked immunosorbent assay (ELISA), hematoxylin-eosin staining, Masson staining, immunofluorescence and qPCR analysis.@*RESULTS@#After high-salt feeding, compared with the control and negative control group, in the model group the blood pressure increased significantly, the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were significantly reduced, and the serum NT-proBNP concentration increased significantly (all P<0.05); furthermore, the arrangement of myocardial cells was disordered, the edema was severe, and the degree of myocardial fibrosis was also significantly increased (P<0.05); the protein and mRNA expressions of collagen type I (Col I) were up-regulated (P<0.05), and the mRNA expressions of transforming growth factor β 1 (TGF- β 1), Smad2 and Smad3 were significantly up-regulated (P<0.05). Compared with HF group, after intervention of Shenmai Injection, LVEF and LVFS increased, myocardial morphology was improved, collagen volume fraction decreased significantly (P<0.05), and the mRNA expressions of Col I, TGF- β 1, Smad2 and Smad3, as well as Col I protein expression, were all significantly down-regulated (all P<0.05).@*CONCLUSION@#Myocardial fibrosis is the main pathological manifestation of hypertensive heart failure, and Shenmai Injection could inhibit myocardial fibrosis and effectively improve heart failure by regulating TGF-β 1/Smad signaling pathway.

Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β1/Smad Signal Pathway / 中国实验方剂学杂志

Objective:To study the protective effect of Xiayuxue Tang on adenine-induced renal fibrosis model in rats and its impact on Wnt/<italic>β</italic>-catenin and transforming growth factor <italic>β</italic>₁（TGF-<italic>β</italic>₁）/Smad signal pathway. Method:A total of 50 SPF-grade male SD rats were randomly divided into 5 groups： the normal group， the model group， the losartan group （9 mg·kg^-1） and low and high dose （2.43，4.86 g·kg^-1） of Xiayuxue Tang groups. The rat model of renal fibrosis was established by ig administration adenine （250 mg·kg^-1） for 24 consecutive days. The rats were then given the corresponding drugs for 30 consecutive days. The levels of serum creatinine（SCr） and blood urea nitrogen （BUN） were measured by enzyme-linked immunosorbent assay（ELISA）. The histopathological changes of renal tissues in rats were observed by hematoxylin and eosin （HE） staining. The collagen deposition in rat renal tissue was observed by Masson staining； the protein expression levels of Wnt5a， Wnt5b， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁， Smad4， Smad7 in renal tissue were detected respectively by immunohistochemistry（IHC） and Western blot. Result:Compared with the normal group， the results of each experimental group showed that SCr and BUN levels significantly increased in the model group （<italic>P</italic><0.01）. SCr and BUN levels decreased significantly after the intervention with the Xiayuxue Tang （<italic>P</italic><0.01）. Compared with the normal group， HE and Masson staining results showed that rats in the model group had severe renal interstitial damage and massive deposition of renal interstitial collagen. The renal interstitial tubule injury was relieved after the intervention with the Xiayuxue Tang， and the renal interstitial collagen deposition decreased. The results of IHC and Western blot showed that compared with the normal group， the expressions of Wnt5a， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁ protein in the kidney of rats up-regulated （<italic>P</italic><0.01）， while the expressions of Wnt5b and Smad7 protein down-regulated （<italic>P</italic><0.01）. After the intervention with Xiayuxue Tang， the expressions of Wnt5a， <italic>β</italic>-catenin， TGF-<italic>β</italic>₁ protein down-regulated （<italic>P</italic><0.01）， while the expressions of Wnt5b and Smad7 protein up-regulated（<italic>P</italic><0.01）. There was no significant difference between the low-dose and high-dose groups with Xiayuxue Tang. Conclusion:Xiayuxue Tang has the protective effect on RIF rats induced by adenine， and its mechanism is related to the inhibition of Wnt/<italic>β</italic>-catenin and TGF-<italic>β</italic>₁/Smad signal pathway.

The potential role of long non-coding RNA Dnm3os in the activation of cardiac fibroblasts / 生物医学工程学杂志

Long non-coding RNA (lncRNA) Dnm3os plays a critical role in peritendinous fibrosis and pulmonary fibrosis, but its role in the process of cardiac fibrosis is still unclear. Therefore, we carried out study by using the myocardial fibrotic tissues obtained by thoracic aortic constriction (TAC) in an early study of our group, and the

Effects of hydrogen sulfide on renal fibrosis in diabetic rats and its mechanism / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of hydrogen sulfide (HS) on renal fibrosis in diabetic rats and explore its mechanism.@*METHODS@#Male Sprague-Dawley rats were randomly divided into normal control (NC) group, a diabetic control (DC) group, diabetes mellitus (DM)+sodium hydrosulfide (NaHS) group and DM+DL-propargylglycine (PAG) group, with 8 rats in each group.Type 1 diabetes was induced in the respective groups by a single intraperitoneal (i.p.) injection of streptozotocin.From the fifth week, rats in the DM+NaHS and DM+PAG groups were injected (i.p.) with 56 μmol/kg NaHS and 40 mg/kg PAG once a day, respectively.After treatment for 4 weeks, the levels of fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (SCr) were detected.The deposition of renal collagen fibers was observed by Masson staining, and collagen volume fraction (CVF) was calculated.The ultrastructural change of renal tissue was observed by transmission electron microscopy.The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hydroxyproline (Hyp) in renal tissues were detected using the kits.The expression levels of TGF-β1, Smad3, phosphorylated (p)-Smad3 and collagen-IV (col-IV) in renal tissues were detected using Western blot.@*RESULTS@#Compared with the NC group, the levels of FBG, BUN, SCr, CVF, IL-1β, IL-6, TNF-α and Hyp were increased; the deposition of renal collagen fibers and the ultrastructural damage were aggravated; the levels of TGF-β1, Smad3, p-Smad3, p-Smad3/Smad3 and col-IV were increased in the DC group.Compared with the DC group, excluding FBG, the aforementioned indices were improved in the DM+NaHS group; the aforementioned indices were further aggravated in the DM+PAG group.@*CONCLUSIONS@#HS attenuated renal fibrosis in diabetic rats, and the mechanism might be associated with the reduction of the release of proinflammatory cytokines, downregulation of the TGF-β1/Smad3 pathway, and inhibition of excessive accumulation of col-IV.

Pine bark extract (Pycnogenol®) suppresses cigarette smoke-induced fibrotic response via transforming growth factor-β1/Smad family member 2/3 signaling / 한국실험동물학회지

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of Pycnogenol® (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth factor-β1 (TGF-β1) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in TGF-β1/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.