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ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance （CMR） imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine， Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group （33 cases） and an observation group （33 cases） by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition， the control group was treated with placebo granules， and the observation group with Shengmaisan granules for a course of 6 months. The baseline data， clinical efficacy， TCM symptom scores， serological indicators ［high-sensitivity C-reactive protein （hs-CRP）， soluble growth stimulation expressed gene 2 protein （sST2）， pro-collagen Ⅲ N-terminal peptide （PⅢNP）， interleukin （IL）-6， IL-11， transforming growth factor-β1 （TGF-β1）］， echocardiography ［Left atrial diameter （LAD）， left ventricular end systolic diameter （LVEDs）， left ventricular end diastolic diameter （LVEDd）］ and CMR indicators ［left ventricular ejection fraction （LVEF）， myocardial extracellular volume fraction （ECV）， and longitudinal relaxation time （T1）］ were compared between the two groups. ResultFinally， 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment， the scores of TCM symptoms （shortness of breath， fatigue， palpitations， spontaneous or night sweats， thirst/dry throat， feverish feeling in palms and soles， and edema in lower limbs）， total score of TCM symptoms， ECV， T1， inflammation/fibrosis indicators （hs-CRP， sST2， PⅢNP， IL-6， IL-11， and TGF-β1） in observation group decreased （P<0.05， P<0.01）， and the scores of TCM symptoms （except feverish feeling in palms and soles）， T1， and inflammation/fibrosis indicators in the control group decreased （P<0.05， P<0.01）. After treatment， the observation group had lower scores of TCM symptoms （except feverish feeling in palms and soles and edema in lower limbs）， ECV， T1， and inflammation/fibrosis indicators than the control group （P<0.05， P<0.01）. After treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （80.65%， 25/31） in the control group （Z=2.976， P<0.01）. There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome， Shengmaisan Granules can alleviate the TCM symptoms， reduce inflammation， and inhibit myocardial fibrosis by regulating the TGF-β1/IL-11 signaling axis.
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Objective::To investigate the protective effect of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma (GNC) extracts on myocardial fibrosis in diabetic mice by observing the degree of myocardial fibrosis and collagen types I (Collagen Ⅰ), collagen types Ⅲ (Collagen Ⅲ) and transforming growth factor-β1 (TGF-β1) protein expression in myocardial tissues. Method::A diabetic mice model was induced by streptozotocin (STZ) and high-fat diet. A normal control group was established. According to random number table method, diabetic mice were divided into model group, GNC low-dose and high-dose groups (0.819, 1.638 g·kg-1), and metformin group (150 mg·kg-1). Intragastrical administration was given in all groups, and the mice in normal control group received an equal dose of deionized water once a day for 9 weeks. The myocardial interstitial fibrosis in mice was observed by Masson trichromatic staining. Image-pro plus 6.0 analysis software was used to calculate the ratio of collagen area to total area. Immunohistochemistry was used to detect Collagen I, Collagen Ⅲ and TGF-β1 protein expression in myocardial tissues. The protein expression electrophoresis and gray value levels of Collagen I, Collagen Ⅲ and TGF-β1 in the myocardial tissues were detected by Western blot. Result::The results of Masson staining showed that as compared with the normal control group, the myocardial cells of diabetic mice were hypertrophic and disordered, and the myocardial stroma, especially the blue-stained collagenous fibers around the blood vessels, were heavily deposited and connected to each other in a network (P<0.01). As compared with the model group, the arrangement of myocardial cells was significantly improved in GNC low-dose and high-dose groups and metformin group, and the collagenous fibers in the myocardial stroma were significantly decreased (P<0.05). Immunohistochemistry and Western blot results showed positive expression of Collagen Ⅰ, Collagen Ⅲ and TGF-β1 in myocardial tissues, with significantly increased content of protein expression in diabetic mice (P<0.05, P<0.01). As compared with the model group, the positive protein expression decreased and the protein content tended to be normal in each administration group (P<0.05, P<0.01). Conclusion::High-fat diet combined with STZ can induce myocardial fibrosis in diabetic mice, and increase Collagen I, Collagen Ⅲ and TGF-β1 protein expression. Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma and Chuanxiong Rhizoma extracts can improve myocardial fibrosis in diabetic mice by regulating the expression of Collagen I, Collagen Ⅲ and TGF-β1 protein.
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Objective: To study the effect of Yangxinkang tablets on myocardial fibrosis in mice after heart failure, and to explore its mechanism.Method: The model of chronic heart failure in mice was established by thoracic aorta constriction (TAC). After successful modeling, mice were randomly divided into sham operation group, model group, 3-methyladenine(3-MA,15 mg·kg-1) autophagy inhibitor group, Yangxinkang tablets high, medium, and low dose groups (1 170,585,390 mg·kg-1).The sham operation group received equal volume of distilled water. After 30 days, cardiac ultrasound was performed to collect hemodynamic parameters. Cardiac paraffin slices were stained with Masson to observe the morphological changes and fibrosis of cardiomyocytes. Western blot was used to detect lysosome-associated membrane protein(LAMP), microtubule-associated protein light chain 3 (LC3), Beclin-1 autophagyportein, α-smooth muscle activin(α-SMA),Collagen Ⅰ,Collagen Ⅲ protein expression.Result: As compared with normal group, the left ventricular ejection fraction (LVEF) and fractional shortening(FS) were significantly decreased(PPPα-SMA, Collagen Ⅰ, Collagen Ⅲ, LAMP, LC3, and Beclin-1 were significantly increased in model group (PPPα-SMA,Collagen Ⅰ,Collagen Ⅲ,LAMP,LC3 and Beclin-1 were decreased in 3-MA group, Yangxinkang high and medium dose groups(PConclusion: Yangxinkang tablets can reduce myocardial fibrosis and improve cardiac function in mice with heart failure probably by down-regulating autophagy.
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Objective: To investigate the effect of Kangxianling decoction on renal function and expression of extracellular matrix(ECM) in renal tissue of rats with renal fibrosis induced by 5/6 nephrectomy. Method: Totally 50 SD rats were randomly divided into control group (n=7), sham-operation group (n=7), operation group (n=36). The 5/6 nephrectomized renal fibrosis model was established in operation group. After successful modeling, rats were randomly divided into model group, Kangxianling group and losartan potassium group. The losartan potassium group and the Kangxianling group were given losartan potassium (33.3 g·kg-1) and Kangxianling decoction (21 g·kg-1) every day. The control group, sham-operation group and model group were all treated with equal volume of normal saline. Rats were put to death after 24 weeks of consecutive medication, and renal function, 24 h urine volume and 24 h-Pro quantitation of each group were measured. The expressions of collagen Ⅰ(ColⅠ) and ColⅢ in renal tissues were determined by immunohistochemistry and Western blot. Result: Compared with the normal group and sham-operation group, serum creatinine(SCr), blood urea nitrogen(BUN), 24 h urine volume, 24 h-Pro quantitation, renal tissue ColⅠ and ColⅢ expression levels were significantly increased in the model group (PPPConclusion: Kangxianling decoction can down-regulate the expressions of ColⅠ and ColⅢ in kidney tissue, there by inhibiting the accumulation of ECM, and exerting the effect in delaying renal fibrosis and protecting renal function.
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To improve collagen production by recombinant Pichia pastoris, we applied Placket-Burman and Box-Behnken design to optimize the fermentation medium. Through Placket-Burman design, three variables in the medium (concentration of yeast extract, peptone and glycerol) were selected for having significant effect on cell dry weight. Through Box-Behnken design regression coefficients analysis, a secondary degree polynomial equation was established, and the optimum levels of the three variables were yeast extract 1.13%, peptone 1.61% and glycerol 0.86%. During the growth period, an average cell dry weight of 4.41 g/L was obtained after 12 h fermentation, increased by 26%. Through high density fermentation, the production of recombinant human collagen (Ⅲ) was up to 4.71 g/L in 22 L fermentor. The recombinant human collagen (Ⅲ) exhibited good results to repair acetic acid induced gastric ulcer in rats.
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Aim To investigate the effect of thioester-ase superfamily member 4(THEM4)expression on col-lagen secretion in human renal proximal tubular epithe-lial cells (HKC)treated with high glucose. Methods In order to examine the direct effect of THEM4 ex-pression vector on PI3K/ Akt pathway and collagen se-cretion,pYr-ads-4-THEM4 expression vector was con-structed and transfected into the HKC with lipo-fectamine 2000 in vitro. HKC cells were randomly di-vided into four groups:normal glucose group (Con-trol),high glucose group (HG),high glucose plus pYr-ads-4-THEM4 vector group (HG + THEM4 vec-tor) and high glucose plus pYr-adshuttle-4 vector group (HG + V vector). After 48 h with HG stimula-tion,the cells were collected for extraction of protein and phospho-Akt (Ser 473),THEM4,TGF-β1 andα-SMA protein expression were examined by Western blot and immunofluorescence staining respectively. Col Ⅰ and Col Ⅲ were detected using the competitive sandwich ELISA kit according to the manufacturer's instructions. Results High glucose inhibited THEM4 expression,and induced increased phospho-Akt (Ser 473),TGF-β1,α-SMA and secreted ColⅠand secre-ted Col Ⅲ in HKC cells. Up-regulation of THEM4 re-versed high glucose-induced decreased THEM4,in-creased phospho-Akt (Ser 473),TGF-β1,α-SMA, secreted Col Ⅰ and secreted Col Ⅲ in HKC cells. Conclusion The up-regulation of THEM4 may de-crease Col Ⅰ and Col Ⅲ secretion by inhibiting the phosphorylation of Akt and down-regulating the expres-sion of TGF-β1 and α-SMA in high glucose-induced HKC cells.
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AIM:To explore the effects of chloroquine (CQ) on collagen Ⅰ and collagen Ⅲ expression in activated rat hepatic stellate cell line HSC-T6 and the possible mechanism.METHODS:Transforming growth factor-β1 (TGF-β1) was used to activate HSC-T6 cells and 3 doses of CQ was administered for 24 h.The cells were divided into 5 groups as follows:control group,TGF-β1 group,TGF-β1 + CQ (15 μmol/L) group,TGF-β1 + CQ (30 μ mol/L) group and TGF-β1 + CQ (60 μmol/L) group.Western blot was used to determine the expression of LC3-Ⅱ/LC3-Ⅰ,P62 and o-SMA in activated HSC-T6 cells.The expression of collagen Ⅰ and collagen Ⅲ was detected by immunocytochemical staining,Western blot and RT-qPCR.Western blot and RT-qPCR were also used to detect the expression of matrix metalloproteinase-13 (MMP-13),tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 at mRNA and protein levels.RESULTS:The ratio of LC3-Ⅱ / LC3-Ⅰ and P62 expression were increased after CQ intervention.Moreover,they were significantly higher in the TGF-β1 + CQ groups than those in TGF-β1 group (P ＜ 0.01).The expression of collagen Ⅰ and collagen Ⅲ at mRNA and protein levels was significantly increased in all TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.01),and it was markedly increased among TGF-β1 + CQ groups in a dose-dependent manner.The expression of MMP-13 at mRNA and protein levels was significantly lowered and that of TIMP-1 and TIMP-2 was significantly increased in TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.05).CONCLUSION:Inhibition of autophagy by CQ in activated HSC-T6 cells up-regulates the expression of collagen Ⅰ and collagen Ⅲ in a dose-dependent way,probably due to reduction of MMP-13 and enhancement of TIMP-1 and TIMP-2 expression.
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AIM:To explore the effects of chloroquine (CQ) on collagen Ⅰ and collagen Ⅲ expression in activated rat hepatic stellate cell line HSC-T6 and the possible mechanism.METHODS:Transforming growth factor-β1 (TGF-β1) was used to activate HSC-T6 cells and 3 doses of CQ was administered for 24 h.The cells were divided into 5 groups as follows:control group,TGF-β1 group,TGF-β1 + CQ (15 μmol/L) group,TGF-β1 + CQ (30 μ mol/L) group and TGF-β1 + CQ (60 μmol/L) group.Western blot was used to determine the expression of LC3-Ⅱ/LC3-Ⅰ,P62 and o-SMA in activated HSC-T6 cells.The expression of collagen Ⅰ and collagen Ⅲ was detected by immunocytochemical staining,Western blot and RT-qPCR.Western blot and RT-qPCR were also used to detect the expression of matrix metalloproteinase-13 (MMP-13),tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 at mRNA and protein levels.RESULTS:The ratio of LC3-Ⅱ / LC3-Ⅰ and P62 expression were increased after CQ intervention.Moreover,they were significantly higher in the TGF-β1 + CQ groups than those in TGF-β1 group (P ＜ 0.01).The expression of collagen Ⅰ and collagen Ⅲ at mRNA and protein levels was significantly increased in all TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.01),and it was markedly increased among TGF-β1 + CQ groups in a dose-dependent manner.The expression of MMP-13 at mRNA and protein levels was significantly lowered and that of TIMP-1 and TIMP-2 was significantly increased in TGF-β1 + CQ groups as compared with TGF-β1 group (P ＜0.05).CONCLUSION:Inhibition of autophagy by CQ in activated HSC-T6 cells up-regulates the expression of collagen Ⅰ and collagen Ⅲ in a dose-dependent way,probably due to reduction of MMP-13 and enhancement of TIMP-1 and TIMP-2 expression.
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Aim To investigate the effect of magnesi-um isoglycyrrhizinate (MgIG)on radiation -induced pulmonary fibrosis in mice and the mechanism.Meth-ods Fifty female C57BL/6 mice were randomly divid-ed into control group,irradiation (RT)group,MgIG group,RT +MgIG group and RT +dexamethasone (DXM)group,with 1 0 mice in each group.Except for control group and MgIG group,the remaining mice were given a single 1 5Gy 60 Co γray on whole lung. The mice in each group were administered 2 h before irradiation and each day after irradiation:MgIG group and RT +MgIG group were administered with MgIG (1 00 mg·kg -1 )by intraperitoneal injection;control group and RT group were administered with normal sa-line (20 mL·kg -1 )by intraperitoneal injection;RT+DXMgroup was administered with DXM(0.5 mg· kg -1 )by intraperitoneal injection.After 1 2 weeks,the mice were sacrificed and lung tissues were taken out. The degree of alveolitis and pulmonary fibrosis were observed by HE staining and Masson staining.The ex-pressions of type Ⅰ collagen,type Ⅲ collagen and TGF-β1 protein were detected by immunohistochem-isty.Results The alveolitis,pulmonary fibrosis and expressions of type Ⅰ collagen,type Ⅲ collagen, TGF-β1 ,p-Smad2,p-Smad3 increased significantly in RT group compared with control group (P <0.05 ), and were significantly lower in RT +MgIG group and RT +DXMgroup than those in RT group(P <0.05). Conclusion MgIG can improve radiation-induced pulmonary fibrosis in mouse lung tissue,and its mech-anism may be related to the influence of MgIG on TGF-βsignaling pathway.
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Objective To investigate the role of Rho kinase on collagen(COL)Ⅰ and Ⅲ expression of human renal tubular epithelial cells .Methods Human kidney tubular epithelial (HK‐2) cells were cultured in the RPMI‐1640 culture solution containing 15% fetal bovine serum .After 30 min pretreatment by the ALD receptor antagonist eplerenone(10 μmol/L) and Rho kinase inhibi‐tor Y27632(1 μmol/L) ,100 nmol/L ALD acted the HK‐2 cells for 24 h .The expressions of collagenⅠ and Ⅲ mRNA in each group were detected by real time PCR and the expression levels of COL Ⅰ ,Ⅲ and Rho kinase protein were detected by ELISA .Results ALD could up‐regulate the expressions of COLⅠ ,Ⅲ mRNA in HK‐2 cells ,and increased the levels of Rho kinase ,COLⅠ and Ⅲprotein ,while the Rho kinase inhibitor Y27632 and ALD receptor inhibitor eplerenone could antagonize these effects .Conclusion ALD could activate Rho kinase signal transduction pathway in HK‐2 cells and accelerate the progression of tubular interstitial fibro‐sis via Rho kinase induced expression of COL Ⅰ and Ⅲ .
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Objective To observe the prevention and treatment of the total flavonoids from Litchi chinensis Sonn( TFL) on hepatic fibrosis induced by dimethylnitrosamine(DMN)in rats, and to explore its mechanism. Methods Ninety SD rats were randomly divided into six groups, normal control group, model control group, colchicine group, high-, medium- and low-dose TFL group(n=15).Expect for normal control group, the other groups were given intraperitoneal injection of 2 mL.kg-1 of 5% dimethylnitrosamine for 4 weeks as the model group. The rats in the normal control group and model control group were given 5 mL.kg-1of 0.9% sodium chloride solution, colchicine group was treated with 0.1 mg.kg-1 colchicine.High-, medium-and low-dose TFL groups were given 200, 100 and 50 mg.kg-1 of TFL.The rats were sacrificed and the livers were harvested and stained with HE and Masson staining to observe pathological changes and liver fibrosis in the same part 6 weeks after all the medicine was given to the rats each day. Immunohistochemistry and Western blotting were used to detect the expression of the transforming growth factor β-Ⅰ/type Ⅱ receptor ( TβRⅠ/Ⅱ) , collagen Ⅰ( Col Ⅰ) and Ⅲ collagen ( Col Ⅲ) . Results Compared with the normal control group, the semiquantitative score of liver fiber and the protein expression of TβRⅠ, TβRⅡ, ColⅠ and Col Ⅲ in the model control group were significantly increased(P<0.01).Compared with the model control group, the protein expression levels of TβR, TβRⅡ, ColⅠand ColⅢwere significantly decreased( P<0.01) in the high-,medium-and low-dose TFL group.The semiquantitative score of liver fiber was significantly decreased( P<0.01) with a dose-effect relationship. Conclusion TFL can inhibit formation of DMN-induced liver fibrosis in rats, which may be related with reduction of expression of TβRⅠ/Ⅱ of hepatic fibrosis promoting factor TGF-β1 , inhibition of the activation and increase of hepatic stellate cells, reduction of the collagen content.
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Objective To investigate the effect of dihydroartemisinin on pulmonary fibrosis and its mechanism in rats.Methods Seventy-five SD rats were randomly divided into 5 groups:the control group,the model group,the high dihydroartemisinin group,the low dihydroartemisinin group,and the prednisone group(15 rats in each group).Saline(9 g/L,0.3 mL) was injected into the rat trachea of the control group,and the rats of the rest 4 groups were injected bleomycin(3 mg/kg).The rats in the control group and the model group received saline lavage (9 g/L,3 mL),while the rats in the high dihydroartemi-sinin group and the low dihydroartemisinin group received dihydroartemisinin lavage (100,50 mg/kg),and the rats in the prednisone group received prednisone lavage each day.Five rats in each group were sacrificed and lung tissues were removed on the 8th,15th,and 29th day of lavage,and the degree of inflammation in lung tissue was observed by HE staining.The deposit of collagen in lung tissue was observed by Masson staining.The expressions of transforming growth factor β1 (TGF-β1),collagen Ⅰ and collagen Ⅲ in pneumonic tissues were detected by immunohistochemistry.Results The degree of inflammation in pneumonic tissues in the high dihydroartemisinin group,the low dihydroartemisinin group,and the prednisone group were less significantly than that in the model group(all P ＜ 0.01).The deposit of collagen in lung tissues in the model group was obviously increased than that of the control group at each time points(all P ＜0.01).The deposit of collagen in lung tissues in the high dihydroartemisinin group,the low dihydroartemisinin group and the prednisone group were lower than that in the model group(all P ＜0.01),and higher than that of the control group at each time points(all P ＜0.01).There was no significant difference between the high dihydroartemisinin group and the prednisone group (P ＞ 0.05).TGF-β1,collagen Ⅰ and collagen Ⅲ in lung tissues in the high dihydroartemisinin group and the prednisone group were lower than those in the model group(P ＜0.01),and higher than those in the control group at each time points(all P ＜ 0.01).There was no significant difference in TGF-β1,collagen Ⅰ and collagen Ⅲ in lung tissue between the high dihydroartemisinin group and the prednisone group(all P ＞0.05),except that collagen Ⅲ expression in lung tissues was lower than that of the prednisone group on the 29th day (P ＞ 0.05).Conclusions Dihydroartemisinin can lessen the extent of pulmonary fibrosis in rats and its anti-fibrosis effect is dose-dependent.The anti-fibrosis effect of dihydroartemisinin may decrease the deposit of collagens in the lung tissues by inhibiting TGF-β1 expression in the lung tissues and have an effect of antifibrosis.
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Objective To investigate the effect and mechanism of exogenous IGFBPrP1 on collagen content in liver tissue. Methods Twenty-four male C57BL/6 wild-type mice were randomly divided into three groups: Control group (n=8), rmIGFBPrP1 2 weeks group (n=8) and rmIGFBPrP1 4weeks group (n=8). Both hematoxylin-eosin (HE) staining and picric acid-Sirius red staining were performed. The protein expression of IGFBPrP1, Collagen Ⅰ , Collagen Ⅲ, FN, TGF-β1, Smad3 andp-Smad2/3 was evaluated by immunohistochemistry or Western blot. Results Exogenous IGFBPrP1 can cause pathological changes in liver tissue. Collagen content was significantly increased by hematoxylin-eosin (HE) staining and picric acid-Sirius red staining (P＜0.05). The protein expression of IGFBPrP1, FN and Collagen Ⅰ was gradually increased after rmIGFBPrP1 injection for 2 weeks and 4 weeks by Western blot (P＜0.01). The protein expression of Collagen Ⅲ was obviously increased in the rmIGFBPrP1 2 weeks group and rmIGFBPrP1 4 weeks group by immunohistochemistry, and the level in the 4 weeks group was higher than that in the 2 weeks group (P＜0. 01). The protein expression of TGF-β1, Smad3 and p-Smad2/3 in liver tissue was significantly increased after rmIGFBPrP1 injection in a time-dependent manner by both immunohistochemistry and Western blot (P＜0. 01).Conclusion Exogenous IGFBPrP1 can cause a marked increase in collagen content and the excessive deposition of ECM through the TGF-β1/Smad3 pathway in liver tissue.
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Objective To investigate the protective effect of insulin glargine in myocardium of diabetic rats. Methods Male Wistar rats were randomly divided into normal control group (NC), diabetes mellitus group After 6 weeks, we weighed rats and calculated the heart body weight ratio (H/B), Immunohistochemical technique was used to estimate the expression of transforming growth factor beta 1 (TGF-β_1) and the type-Ⅲ collagen (collagen Ⅲ). Myocardial pathologic changes were observed under expression of TGF-β_1 and collagen Ⅲ of DM group and DI group were significantly higher than those in NC group (P<0.05); the levels of H/B and the expression of TGF-β_1 and collagen Ⅲ of DI group were lower than myofibrils were arranged disorderly, mitochondria increased, with swelling and degeneration, while the changes of myocardial ultrastructure were obviously lightened after treatment with insulin glargine. Conclusion Insulin glargine may partly suppress the increased expression of TGF-β_1 and collagen Ⅲ in myocardial of diabetic rats, and it may decrease significantly the myocardial injury of diabetic rats.
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Objective:This study was to study effect of keeping ying and weiqi in balance on cardiac muscular collagen Ⅰ,collagen Ⅲ,angiotensinⅡ in spontaneous diabetes rats,and provide new thoughts for prevention and treatment for diabetic cardiomyopathy.Methods:40 spontaneous diabetes rats were divided into four groups at random:spontaneous diabetes control group,diformin group,Guizhi Decoction group and Huanglian Jiedu Decoction group.Except control group,each group was given intragastric administration for 12weeks.Blood glucose,collagenⅠ,collagen Ⅲ,collagenⅠ/collagen Ⅲ,angiotensin Ⅱ were determined.Euzymelinked immunosorbent assay and radio-immuniy method were used.Results:Blood glucose in Huanglian Jiedu Decoction group and diformin group decreased;Compared respectively with diformin group and control group,collagenⅠdecreased obviously and collagen Ⅲ increased signifi cantly in Guizhi Decoction group,and the collagenⅠ/collagen Ⅲ decreased.Compared with diformin group and control group,cardiac muscular homogenate AT-Ⅱ contents decreased in both of Guizhi Decoction group and Huanglian Jiedu Decoction group.Conclusion:Guizhi Decoction can decrease the content of collagen Ⅰ,AT-Ⅱ and collagenⅠ/collagen Ⅲin cardiac muscular,and increase content of collagen Ⅲ,then prevent and treat cardiac muscular collagen reconstruction and myocardial fibrosis.Huanglian Jiedu Decoction can decrease the content of AT-Ⅱ,and decrease collagenⅠ/ collagen Ⅲ,collagenⅠ slightly,and can improve cardiac muscular collagen reconstruction.Keeping ying and weiqi in balance is a new thought for prevention and treatment for diabetic cardiomyopathy.
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Objective On the basis of the lasted clinical experience,our group will discuss the treatmented mechanism of Chinese herb kang-xian-er-hao(KXEH) ameliorate hepatic cirrhosis. Methods Male wistar rats were divided into five groups,excepted for normal group N,the remnant four groups were all given intraperitoneal injection of porcine serum((0.5) ml/time,2 times/week,total 12 weeks).In KXEH early treatment group B,the rats were fed with KXEH by gavage,1 g/100 g,once a day at the third week.In KXRH late treatment group C,the rats were fed with KXEH by gavage,1 g/100 g,once a day at the ninth week.In ?-interferon treated group D the rats were subcutaneous injection ?-interferon((0.1) million) every day at the ninth week.The model group A and normal group N were fed with the same amount of saline by gavage.The rats were killed at the end of the twelfth weeks,the formation of liver fibrosis was observed with HE stain and Masson stain.The expression of Smooth muscle actin(SMA) was observed by immunohistochemistry.As well as SMA,collagen Ⅰ、Ⅲ mRNA and Smad3 mRNA,which is TGF-?1 downstream signal,were detected in liver samples with RT-PCR assay. Results In KXEH treated group B and C,the body weight was heavier,the size of liver and spleen was smaller and the ratio of liver weight/body weight and spleen weight/body weight was decreased compared with the model group A(P
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AIM: To study the role of p38 mitogen-activated protein kinase (p38MAPK) activation in high glucose-induced collagen Ⅲ synthesis in NRK52E cells. METHODS: Normal rat tubular epithelial cell line NRK52E was cultured in D-glucose of different concentrations, pretreated with SB203580 and collected at different time points. The levels of phospho-p38MAPK and extracellular matrix collagen Ⅲ were examined by Western blotting. RESULTS: The activation of p38MAPK was shown to be dependent upon D-glucose concentration and the time-course. Pretreatment with SB203580 blocked p38MAPK activation induced by high concentration of D-glucose in NRK52E cells. CONCLUSIONS: The activation of p38MAPK induced by high concentration of glucose may play a role in diabetic interstital renal fibrosis. SB203580 has a potential value of clinical applications in the prevention and treatment of diabetic nephropathy.
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Objective To investigate into the protective effects of rosiglitazone on rat kidney fibroblasts(NRK)damaged by high glucose.Methods From Jan.2005 to Sep.2005,the NRK cells were cultured in vitro,and were divided into five groups:normal glucose group(NG,1 000 mg/L D-glucose),high glucose group(HG,4 500 mg/L D-glucose),HG+RGZ(5 ?mol/L),HG+RGZ(10 ?mol/L)and HG+RGZ(15 ?mol/L).The mRNA expressions of T MMP-1、TIMP-1 and Collagen Ⅲ were measured with RT-PCR.Results Compared with NG group,the mRNA expression of MMP-1 decreased markedly in HG group(P
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Objective To study the role of ligustrazine injection on collagen-Ⅲ(Col-Ⅲ) and laminin(LN) in pulmonary fibrosis rats induced by bleomycin A5.Methods Seventy Wistar rats were divided into 5 groups at random:normal group,model group,large-dose group,middle-dose group,little-dose group.The other groups were injected bleomycin A5 in intratrache except for normal group.From the second day,large-dose group,middle-dose group,little-dose group were given ligustrazine injection by intraperitoneal injection to 28th day,the dose was dividedly:250,150,40 mg/(kg?d).Col-Ⅲ and LN in serum were detected in 14th,28th days and the content of them in lung tissue homogenate in 28th day were also detected.HE staining was detected on lung tissue.Results The contents of Col-Ⅲ and LN of lung tissue and serum in pulmonary fibrosis rats were significantly upgraded compared with that of normal group(P
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AIM:To investigate the effect of Rehmannia glutinosa Libosch on collagen Ⅰ and Ⅲ of in pulmonary interstitial fibroblast in rat. METHODS: The components of Radix Rehmanniae were extracted and isolated to several parts.Primary pulmonary fibroblasts were separated from lung interstitial tissue of rat.After being reproduced for several generations,fibroblasts were cultured in the extracts of Radix Rehmanniae and Shengdi Solution for injection in several concentrations respectively for 72 hours,and then contents of Col Ⅰ and Col Ⅲ of these fibroblast were determined by RT-PCR. RESULTS: The part containing mainly oligosaccharide from preparation that decocted with water and deposited with alcohol could inhibit Col Ⅰ with a few exceptions concentration while it could inhibit Col Ⅲ at high concentration.The part of deposit inhibited Col Ⅰ obviously in the concentration of 2?10~(-2) g/mL and could inhibit Col Ⅲ in all the concentrations.Shengdi Solution for injection could inhibit Col Ⅲ in all the concentrations. CONCLUSION: Some constitutents of Radix Rehmanniae can inhibit the expression of Col Ⅰ and Col Ⅲ of pulmonary fibroblast which is one of mechanisms that Radix Rehmanniae takes effect on fibrosis disease in pulmonary interstitial tissue.