• The Korean Journal of Physiology and Pharmacology
• /
• 제25권2호
• /
• pp.131-137
• /
• 2021

Aging is the process spontaneously occurred in living organisms. Cardiac fibrosis is a pathophysiological process of cardiac aging. Mangiferin is a well-known C-glucoside xanthone in mango leaves with lots of beneficial properties. In this study, rat model of cardiac fibrosis was induced by injected with 150 mg/kg/d D-galactose for 8 weeks. The age-related cardiac decline was estimated by detecting the relative weight of heart, the serum levels of cardiac injury indicators and the expression of hypertrophic biomakers. Cardiac oxidative stress and local inflammation were measured by detecting the levels of malondialdehyde, enzymatic antioxidant status and proinflammatory cytokines. Cardiac fibrosis was evaluated by observing collagen deposition via masson and sirius red staining, as well as by examining the expression of extracellular matrix proteins via Western blot analysis. The cardiac activity of profibrotic TGF-β1/p38/MK2 signaling pathway was assessed by measuring the expression of TGF-β1 and the phosphorylation levels of p38 and MK2. It was observed that mangiferin ameliorated D-galactose-induced cardiac aging, attenuated cardiac oxidative stress, inflammation and fibrosis, as well as inhibited the activation of TGF-β1/p38/MK2 signaling pathway. These results showed that mangiferin could ameliorate cardiac fibrosis in D-galactose-induced aging rats possibly via inhibiting TGF-β/p38/MK2 signaling pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• 제26권2호
• /
• pp.87-94
• /
• 2022

Myocardial infarction promotes cardiac remodeling and myocardial fibrosis, thus leading to cardiac dysfunction or heart failure. Peiminine has been regarded as a traditional anti-fibrotic Chinese medicine in pulmonary fibrosis. However, the role of peiminine in myocardial infarction-induced myocardial injury and fibrosis remained elusive. Firstly, rat model of myocardial infarction was established using ligation of the left coronary artery, which were then intraperitoneally injected with 2 or 5 mg/kg peiminine once a day for 4 weeks. Echocardiography and haemodynamic evaluation results showed that peiminine treatment reduced left ventricular end-diastolic pressure, and enhanced maximum rate of increase/decrease of left ventricle pressure (± dP/dt max) and left ventricular systolic pressure, which ameliorate the cardiac function. Secondly, myocardial infarction-induced myocardial injury and infarct size were also attenuated by peiminine. Moreover, peiminine inhibited myocardial infarction-induced increase of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α production, as well as the myocardial cell apoptosis, in the rats. Thirdly, peiminine also decreased the myocardial fibrosis related protein expression including collagen I and collagen III. Lastly, peiminine reduced the expression of p38 and phosphorylation of extracellular signal-regulated kinase 1/2 in rat model of myocardial infarction. In conclusion, peiminine has a cardioprotective effect against myocardial infarction-induced myocardial injury and fibrosis, which can be attributed to the inactivation of mitogen-activated protein kinase pathway.

• Journal of Korean Neurosurgical Society
• /
• 제66권5호
• /
• pp.503-510
• /
• 2023

Objective : The present study aimed to determine the topical and systemic efficacy of tranexamic acid (TXA) on epidural fibrosis in a rat laminectomy model. Methods : Thirty-two 12-month-old adult Sprague-Dawley rats were used in this study. Each rat underwent bilateral laminectomy at the L1 and L2 vertebral levels. Rats were divided into four groups : in group I (control group, n=8), a laminectomy was performed and saline solution was applied into the surgical space. In group II (topical group, n=8), laminectomy was performed and 30 mg/kg TXA was applied to the surgical site before skin closure. In group III (systemic group, n=8), 30 mg/kg TXA was administered intravenously via the tail vein in the same session as the surgical procedure. In group IV (topical and systemic group, n=8), TXA was administered 30 mg/kg both topical and intravenous. The rats were sacrificed at 4 weeks postoperatively. Masson's trichrome and hematoxylin and eosin were used to assess acute inflammatory cells, chronic inflammatory cells, vascular proliferation, and epidural fibrosis. Results : Epidural fibrosis, acute inflammation, chronic inflammation, and sum histologic score value were significantly lower in the systemic TXA group, systemic and topical TXA groups than in the control group (p<0.05). In addion, the sum histologic score was significantly lower in the topical TXA group than in the control group (p<0.05). Conclusion : In this study, epidural fibrosis formation was prevented more by systemic application, but the topical application was found to be effective when compared to the control group. As a result, we recommend the systemic and topical use of TXA to prevent epidural fibrosis during spinal surgery.

• Tuberculosis and Respiratory Diseases
• /
• 제67권5호
• /
• pp.436-444
• /
• 2009

Background: Micro computed tomography (CT) is rapidly developing as an imaging tool, especially for mice, which have become the experimental animal of choice for many pulmonary disease studies. We evaluated the usefulness of micro CT for evaluating lung fibrosis in the murine model of bleomycin-induced lung inflammation and fibrosis. Methods: The control mice (n=10) were treated with saline. The murine model of lung fibrosis (n=60) was established by administering bleomycin intra-tracheally. Among the 70 mice, only 20 mice had successful imaging analyses. We analyzed the micro CT and pathological findings and examined the correlation between imaging scoring in micro CT and histological scoring of pulmonary inflammation or fibrosis. Results: The control group showed normal findings on micro CT. The abnormal findings on micro CT performed at 3 weeks after the administration of bleomycin were ground-glass opacity (GGO) and consolidation. At 6 weeks after bleomycin administration, micro CT showed various patterns such as GGO, consolidation, bronchiectasis, small nodules, and reticular opacity. GGO (r=0.84) and consolidation (r=0.69) on micro CT were significantly correlated with histological scoring that reflected pulmonary inflammation (p<0.05). In addition, bronchiectasis (r=0.63) and reticular opacity (r=0.83) on micro CT shown at 6 weeks after bleomycin administration correlated with histological scoring that reflected lung fibrosis (p<0.05). Conclusion: These results suggest that micro CT findings from a murine model of bleomycin-induced lung fibrosis reflect pathologic findings, and micro CT may be useful for predicting bleomycin-induced lung inflammation and fibrosis in mice.

• Journal of Ginseng Research
• /
• 제45권3호
• /
• pp.408-419
• /
• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• BMB Reports
• /
• 제50권2호
• /
• pp.58-59
• /
• 2017

The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

• Toxicological Research
• /
• 제22권3호
• /
• pp.267-273
• /
• 2006

Tungtungmadic acid(3-caffeoyl, 4-dihydrocaffeoyl quinic acid: CDCQ) is a new chlorogenic acid derivative isolated from the Salicornia herbacea. The suppressive effects of CDCQ on the progress of acute carbon tetrachloride($CCl_4$)-induced hepatic fibrosis were investigated in mice. CDCQ significantly suppressed $CCl_4$-induced hepatic necrosis and inflammation, as determined by serum enzymatic activities of alanine and aspartate aminotransferase and serum TNF-$\alpha$ levels in a dose-dependent manner. In addition, increased hepatic lipid peroxidation and fibrosis after acute $CCl_4$ treatment were suppressed by the administration of CDCQ. CDCQ also significantly prevented the elevation of hepatic hydroxyproline and collagen content and ${\alpha}$-smooth muscle actin(${\alpha}$-SMA) expression in the liver of $CCl_4$-intoxicated mice. These results suggest that the suppressive effects of CDCQ against the acute $CCl_4$-induced hepatic fibrosis possibly related to its ability to block both hepatic inflammation and the activation of hepatic stellate cells.

• Journal of Applied Biological Chemistry
• /
• 제59권1호
• /
• pp.25-29
• /
• 2016

B형 간염 바이러스는 간경변증과 간세포암의 원인이 되는 간섬유화를 유발한다. 하지만 현재까지 그와 관련한 자세한 메커니즘은 밝혀지지 않았기에 본 연구에서 이를 알아보고자 하였다. 실험 결과, B형 간염 바이러스에서 발현되는 HBx 단백질에 의해 vimentin, fibronectin, slug, snail, NOX4가 증가되는 것을 확인하였다. NOX4에 의한 활성산소가 snail, slug 발현을 유도하고 섬유화 과정을 촉진할 수 있기 때문에 NOX4의 발현을 유도하는 HBx가 간섬유화를 조절, 유도하는 것을 확인하였다.

• 한국임상수의학회지
• /
• 제21권3호
• /
• pp.280-285
• /
• 2004

Pathological and bacteriological studies were made of a total of 111 udders from slaughtered Korean native cows originating from various locations in Chonnam province. Incidence of supernumerary teats was 8.1%. Gross lesions were found in 21.4% of mucous membranes of total teat cisterns; these lesions comprised epithelial hyperplasia (12.6%), congestion (4.1%), slight fibrosis (3.8%) and severe fibrosis with congestion (0.9%). Gross lesions in the glandular tissues were found in 35.1% of cows; these lesions comprised slight fibrosis (27.9%), moderate fibrosis (6.3%) and severe fibrosis with pus (0.9%). Mastitis was found only in one cow. One hundred and twenty-five strains of microorganisms were isolated from mammary gland fragments of the cows. Pathogens most commonly isolated were Staphylococcus spp.; most of them were minor mammary pathogens. Major mammary pathogens were Streptococcus spp. (9.6%) and E. coli (2.4%). Most of the isolates were susceptible to many of 13 antimicrobial agents used, but Streptococcus spp. and Gram-negative rods showed resistance to 7 and 8 agents, respectively. 97.5% of the isolates showed susceptibility to amoxicillin, but only 55.8% to erythromycin.

• Tuberculosis and Respiratory Diseases
• /
• 제51권4호
• /
• pp.373-378
• /
• 2001

저자들은 애성을 주소로 내원한 60세 남자 환자에서 prednisolone과 tranilast의 투여로 호전된 특발성 종격동 섬유화증 1예를 경험하였기에 문현고찰과 함께 보고하는 바이다.