【摘要】：目的:(1)以年齡、病程無差異的Wilson病(WD)肝纖維化患者作為研究對(duì)象,選用丹參顆粒作為對(duì)照治療方法,觀察肝豆扶木湯(GDFMT)對(duì)WD肝纖維化患者UWDRS肝臟功能評(píng)分、中醫(yī)證候積分值、TGF-β1、TNF-α、IL-6值的影響,評(píng)價(jià)GDFMT治療WD肝纖維化患者的臨床療效及對(duì)相關(guān)生化指標(biāo)的影響。(2)以TGF-β1/smad信號(hào)轉(zhuǎn)導(dǎo)通路為基礎(chǔ),以TX小鼠作為實(shí)驗(yàn)觀察對(duì)象,應(yīng)用可多靶點(diǎn)治療WD肝纖維化的肝豆扶木湯(GDFMT)為干預(yù)藥物,經(jīng)過高、中、低濃度GDFMT不同療程干預(yù)后,采用半定量RT-PCR檢測肝組織中TGF-β1、TβRI、TβRII、Smad2、Smad3、Smad4和Smad7,探討GDFMT抗WD肝纖維化的療效及其通路機(jī)制。方法:臨床部分:將符合WD肝纖維化納入標(biāo)準(zhǔn)的60例患者隨機(jī)分為治療組(GDFMT組)30例,對(duì)照組(丹參組)30例。治療組治療藥物予以GDFMT,對(duì)照組治療藥物予以丹參顆粒,同時(shí)予以2組患者相同的驅(qū)銅補(bǔ)鈣基礎(chǔ)治療,基礎(chǔ)治療以8天作為一個(gè)療程,予以DMPS靜脈驅(qū)銅治療6天,后2天予以補(bǔ)鈣治療,總計(jì)4個(gè)療程。評(píng)價(jià)兩組患者治療前后UWDRS肝臟功能積分值、中醫(yī)證候積分值;并檢測兩組患者TGF-β1、TNF-α、IL-6指標(biāo)變化。實(shí)驗(yàn)部分:192只雄性TX小鼠被隨機(jī)分為以下6組:GDFMT高劑量組、GDFMT中劑量組、GDFMT低劑量組(分別簡稱“高劑量組、中劑量組、低劑量組”)、模型組(生理鹽水)、青霉胺組(青霉胺)、丹參組(丹參);另外以DL小鼠32只為正常對(duì)照組,共7組。予以7組受試動(dòng)物相應(yīng)的藥物處理,每天灌胃1次,連續(xù)56天,分別于灌胃治療后2、4、6、8周結(jié)束時(shí)將受試動(dòng)物分批處死,每組每次8只。采用半定量RT-PCR檢測各周各批TX小鼠肝組織內(nèi)TGF-β1、TβRI、TβRII、Smad2、Smad3、Smad4和Smad7的m RNA相對(duì)表達(dá)量,并作出比較。結(jié)果:(1)臨床部分:臨床總療效:治療4個(gè)療程后,可見治療組臨床總療效明顯優(yōu)于對(duì)照組(P0.01);治療前兩組患者中醫(yī)證候積分值比較無差異(P0.05);兩組患者在治療前UWDRS肝臟功能評(píng)分值無差異(P0.05);兩組分別與同組治療前相比,治療后中醫(yī)證候積分值均降低(P0.01,P0.05);與同組治療前相比,2組治療后UWDRS肝臟功能評(píng)分值均降低,具有統(tǒng)計(jì)學(xué)意義(P0.01,P0.05);2組患者治療后中醫(yī)證候積分值對(duì)比,治療組較對(duì)照組降低更明顯(P0.01);2組患者治療后UWDRS肝臟功能評(píng)分值對(duì)比,治療組治療效果優(yōu)于對(duì)照組(P0.01)。臨床療效性指標(biāo)評(píng)估:血清TGF-β1、TNF-α、IL-6治療前兩組間比較,治療組和對(duì)照組治療前TGF-β1、TNF-α、IL-6值均無差異(P0.05);兩組療前、療后組內(nèi)比較,治療組療后較療前TGF-β1、TNF-α、IL-6均顯著降低(P0.01),對(duì)照組治療后TGF-β1、TNF-α、IL-6較治療前有明顯下降(P0.01,P0.05);治療組、對(duì)照組治療后比較,治療組比對(duì)照組改善更加明顯(P0.01)。綜上比較說明肝豆扶木湯具有良好的抗肝纖維化臨床療效。(2)實(shí)驗(yàn)部分:各組受試動(dòng)物經(jīng)治療2、4、6、8周后的檢驗(yàn)指標(biāo)比較結(jié)果如下:⑴模型組2、4、6、8周與對(duì)應(yīng)的正常組比較,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)值顯著升高,Smad7m RNA相對(duì)值顯著降低(P0.01)。⑵各治療組與對(duì)應(yīng)模型組比較如下:(1)高劑量組、中劑量組、丹參組、青霉胺組2、4、6、8周及低劑量組4、6、8周較對(duì)應(yīng)模型組,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)值均下降,Smad7m RNA相對(duì)值上升(P0.05,P0.01);(2)低劑量組2周較對(duì)應(yīng)模型組無統(tǒng)計(jì)學(xué)差異(P0.05);⑶GDFMT高劑量組與對(duì)應(yīng)GDFMT中、低劑量組、丹參組、青霉胺組比較如下:(1)GDFMT中、低劑量組、丹參組、青霉胺組2、4、6、8周及青霉胺4、6、8周與對(duì)應(yīng)的GDFMT高劑量組比較,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量降低,Smad7m RNA的相對(duì)表達(dá)量升高(P0.05,P0.01);(2)與青霉胺組2周比較,GDFMT高劑量組與其無統(tǒng)計(jì)學(xué)差異(P0.05)。⑷GDFMT中劑量組與丹參組、青霉胺組、低劑量組比較如下:(1)中劑量組與丹參組比較無統(tǒng)計(jì)學(xué)差異(P0.05);(2)與青霉胺組比較,中劑量組2、4周的TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量較其高,Smad7m RNA的相對(duì)表達(dá)量較其低(P0.05,P0.01);青霉胺組與中劑量組6、8周比較,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量降低,Smad7m RNA的相對(duì)表達(dá)量升高(P0.05,P0.01);(3)低劑量與對(duì)應(yīng)中劑量組6、8周比較,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量較其低,Smad7m RNA的相對(duì)表達(dá)量較其高(P0.01);低劑量組2周與對(duì)應(yīng)中劑量比較無差異(P0.05)。⑸丹參組與青霉胺組、低劑量組比較如下:(1)丹參組2、4周較對(duì)應(yīng)青霉胺組TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量較其高,Smad7m RNA的相對(duì)表達(dá)量較其低(P0.05,P0.01);丹參組6、8周較對(duì)應(yīng)青霉胺組TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量降低,Smad7m RNA的相對(duì)表達(dá)量升高(P0.05,P0.01);(2)丹參組6、8周與對(duì)應(yīng)低劑量組比較,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量較其低,Smad7m RNA的相對(duì)表達(dá)量較其高(P0.01);丹參組2周與對(duì)應(yīng)低劑量組比較無差異(P0.05)。⑹青霉胺組與低劑量組比較如下:青霉胺2、4周較對(duì)應(yīng)低劑量組,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量較其低,Smad7m RNA的相對(duì)表達(dá)量較其高(P0.05,P0.01);青霉胺組6周較對(duì)應(yīng)低劑量組無差異(P0.05);青霉胺8周較對(duì)應(yīng)低劑量組,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4的m RNA相對(duì)表達(dá)量較高,Smad7m RNA的相對(duì)表達(dá)量較低(P0.01)。⑺(1)GDFMT高劑量組4周與對(duì)應(yīng)2周相比,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4m RNA相對(duì)值降低,Smad7m RNA相對(duì)值升高(P0.01);(2)GDFMT中、低劑量組4周與對(duì)應(yīng)2周相比,無明顯差異(P0.05)。⑻6周與對(duì)應(yīng)4周比較,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smad4m RNA相對(duì)值降低,Smad7m RNA相對(duì)值升高(P0.01);⑼8周與對(duì)應(yīng)6周比較,TGF-β1、TβRI、TβRII、Smad2、Smad3和Smadm RNA相對(duì)表達(dá)量均降低,Smad7m RNA相對(duì)表達(dá)量則升高(P0.01)。結(jié)論:(1)GDFMT能夠有效地改善WD肝纖維化患者中醫(yī)證候積分及UWDRS肝臟功能評(píng)分,改善其臨床癥狀和體征。(2)GDFMT能夠有效地降低WD肝纖維化患者TGF-β1、TNF-α、IL-6,發(fā)揮抗纖維化的作用。(3)GDFMT使TGF-β1、TβRⅠ、TβRⅡ、Smad2、Smad3、Smad4的m RNA相對(duì)表達(dá)量下降、Smad7m RNA相對(duì)表達(dá)量升高,說明GDFMT能夠調(diào)控TGF-β1/Smad信號(hào)轉(zhuǎn)導(dǎo)通路中的蛋白表達(dá),抑制TGF-β1/Smad信號(hào)傳導(dǎo)通路激活HSC,從而發(fā)揮抗纖維化作用,且對(duì)TGF-β1/Smad信號(hào)傳導(dǎo)的調(diào)控呈量效-時(shí)效依賴性。
[Abstract]:Objective: (1) To observe the effect of Gandou Fumu Decoction (GDFMT) on UWDRS liver function score, TCM syndrome score, TGF-beta 1, TNF-a and IL-6 in patients with Wilson's disease (WD) and liver fibrosis treated with GDFMT. (2) Based on the TGF-beta 1/smad signal transduction pathway and TX mice, Gandou Fumu Decoction (GDFMT) was used as an intervention drug to treat WD hepatic fibrosis. After the intervention of different courses of high, medium and low concentration GDFMT, the liver tissues were detected by semi-quantitative RT-PCR. TGF-beta 1, Tbeta RI, Tbeta RII, Smad 2, Smad 3, Smad 4 and Smad 7 were used to investigate the effect of GDFMT on hepatic fibrosis induced by WD and its mechanism. Shen granules were given the same basic treatment as those in the two groups. The basic treatment was 8 days as a course of treatment. DMPS was given intravenous copper-repelling therapy for 6 days, and calcium-supplementing therapy was given 2 days after treatment for 4 courses. In the experimental part, 192 male TX mice were randomly divided into 6 groups: high dose GDFMT group, middle dose GDFMT group, low dose GDFMT group (abbreviated as "high dose group, middle dose group, low dose group"), model group (saline), penicillamine group (penicillamine), Salvia miltiorrhiza group (Salvia miltiorrhiza), and 32 DL mice as normal control group (7 groups). Seven groups of animals were given corresponding drug treatment once a day for 56 consecutive days. At the end of 2,4,6,8 weeks after the treatment, the animals were sacrificed in batches, 8 in each group. The relative expression of TGF-beta 1, Tbeta RI, Tbeta RII, Smad2, Smad3, Smad4 and S7 in liver tissues of TX mice was detected by semi-quantitative RT-PCR. Results: (1) Clinical part: After four courses of treatment, the total clinical efficacy of the treatment group was significantly better than that of the control group (P After treatment, the scores of TCM syndromes decreased (P 0.01, P 0.05); compared with the same group before treatment, the scores of UWDRS liver function in the two groups after treatment were lower, with statistical significance (P 0.01, P 0.05); after treatment, the scores of TCM syndromes in the two groups were compared, the treatment group was more significantly lower than the control group (P 0.01); after treatment, the scores of UWDRS liver function in the two groups were significantly lower than those in the control group (P 0.01); The therapeutic effect of the treatment group was better than that of the control group (P 0.01). Evaluation of clinical therapeutic indexes: serum TGF-beta 1, TNF-a, IL-6 before treatment were compared between the treatment group and the control group, there was no difference in TGF-beta 1, TNF-a, IL-6 before and after treatment between the two groups (P 0.05); before and after treatment, the treatment group compared with the pre-treatment group, the treatment group TGF-beta 1, TNF-a, IL-6 were significantly reduced (P 0.01). After treatment, TGF-beta 1, TNF-alpha and IL-6 in the control group decreased significantly (P 0.01, P 0.05); after treatment, compared with the control group, the treatment group improved more significantly (P 0.01). To sum up, Gandou Fumu Decoction has a good clinical effect on anti-hepatic fibrosis. (2) Experimental part: The animals in each group were tested after 2, 4, 6, 8 weeks of treatment. The results were as follows: (1) Compared with the corresponding normal group, the relative value of M RNA of TGF-beta 1, Tbeta RI, Tbeta RII, Smad2, Smad3 and Smad 4 in the model group increased significantly at 2, 4, 6 and 8 weeks, and the relative value of Smad7m RNA decreased significantly (P 0.01). (2) The comparison between the treatment groups and the corresponding model group was as follows: (1) High dose group, middle dose group, Salvia miltiorrhiza group, Penicillamine group at 2, 4, 4, 6, 8 weeks and low. Compared with the corresponding model group, the relative value of M RNA of TGF-beta 1, Tbeta RI, Tbeta RII, Smad2, Smad3 and Smad 4 decreased, while the relative value of Smad7m RNA increased (P Compared with the corresponding GDFMT high-dose group, the relative expression of M RNA of TGF-beta 1, T-beta RI, T-beta RII, Smad2, Smad3 and Smad 4 decreased, while the relative expression of Smad7m RNA increased (P 0.05, P 0.01) in the middle, low-dose group, the salvia miltiorrhiza group, the penicillamine group and the penicillamine group at 2, 4, 6, 8 weeks; (2) Compared with the penicillamine group at 2 weeks, there was no significant difference between the high-dose group and the corresponding GDFMT high-dose group (P 0.05). (2) Compared with the Penicillin group, the relative expression of TGF-beta 1, Tbeta RI, Tbeta RII, Smad2, Smad3 and Smad 4 in the middle dose group was higher, and the relative expression of Smad7m RNA was lower (P 0.05, P 0.0). 1) Compared with the medium-dose group, the relative expression of M RNA of TGF-beta 1, Tbeta RI, Tbeta RII, Smad2, Smad 3 and Smad4 decreased, while the relative expression of Smad7m RNA increased (P 0.05, P 0.01); (3) Compared with the corresponding medium-dose group at 6 and 8 weeks, the relative expression of TGF-beta 1, Tbeta RI, Tbeta RII, Smad2, Smad 3 and Smad4 was lower, and the relative expression of Smad7m RNA was lower. The expression of TGF-beta 1, T-beta RI, T-beta RII, Smad2, Smad3 and Smad 4 in the salvia miltiorrhiza group was higher than that in the corresponding penicillamine group at 2 and 4 weeks, and the relative expression of Smad7m RNA was lower than that in the corresponding penicillamine group (P 0.05, P 0.01). Compared with the corresponding penicillamine group, the relative expression of TGF-beta 1, T-beta RI, T-beta RII, Smad2, Smad3 and Smad4 in Danshen group decreased at 6 and 8 weeks, while the relative expression of Smad7m RNA increased (P 0.05, P 0.01); (2) Compared with the corresponding low-dose group at 6 and 8 weeks, the relative expression of TGF-beta 1, T-beta RI, T-beta RII, Smad2, Smad3 and Smad4 was lower, and the relative expression of Smad7m RNA was lower in Danshen group. Compared with the corresponding low-dose group, the relative expression of M RNA of TGF-beta 1, T-beta RI, T-beta RII, Smad2, Smad3 and Smad 4 in the penicillamine group was lower, and the relative expression of Smad7m RNA was higher (P 0.05, P 0.01). Compared with the corresponding low-dose group, there was no significant difference (P 0.05); the relative expression of M RNA of TGF-beta 1, T-beta RI, T-beta RII, Smad2, Smad3 and Smad 4 was higher in the penicillamine group at 8 weeks, and Smad7m RNA was lower in the high-dose group (P 0.01). Relative RNA value increased (P 0.01); (2) In GDFMT, there was no significant difference between the low-dose group and the corresponding two weeks (P 0.05). _Compared with the corresponding four weeks, the relative values of TGF-1, T-beta RI, T-beta RII, Smad2, Smad3 and Smad4m RNA decreased, and the relative value of Smad7m RNA increased (P 0.01); Compared with the corresponding six weeks, the relative tables of TGF-beta 1, T-beta RI, T-beta RI, Smad2, Smad3 and Smad4m RNA increased (P 0.01); _Compared with the corresponding six weeks, the relative tables of TGF Conclusion: (1) GDFMT can effectively improve TCM syndrome score and UWDRS liver function score in patients with WD liver fibrosis, and improve their clinical symptoms and signs. (2) GDFMT can effectively reduce TGF-beta 1, TNF-a, IL-6 in patients with WD liver fibrosis, and play an anti-fibrosis role. (3) GDFMT can make T. GF-beta-1, T-beta-R I, T-beta-R II, Smad2, Smad3, Smad4 relative expression of M RNA decreased, Smad7m RNA relative expression increased, indicating that GDFMT can regulate the expression of protein in the TGF-beta 1/Smad signal transduction pathway, inhibit the TGF-beta 1/Smad signal transduction pathway to activate HSC, thereby playing an anti-fibrosis role, and has a dose-effect on the regulation of TGF-beta 1/Smad signal transduction. Time dependence.
【學(xué)位授予單位】：安徽中醫(yī)藥大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R742.4

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2 張素平;張然;陳峰;張麗霞;陳曄光;;Smad7 antagonises TGF-β signaling in the nucleus[A];中國細(xì)胞生物學(xué)學(xué)會(huì)2005年學(xué)術(shù)大會(huì)、青年學(xué)術(shù)研討會(huì)論文摘要集[C];2005年

3 王劍;楊曉;;Gene expression profile in cardiomyocyte-specific Smad4 knock-out mice[A];中國遺傳學(xué)會(huì)第八次代表大會(huì)暨學(xué)術(shù)討論會(huì)論文摘要匯編（2004-2008）[C];2008年

4 劉昭廷;王強(qiáng);孟安明;;基因組水平上受斑馬魚Smad2調(diào)控的靶基因[A];“細(xì)胞活動(dòng) 生命活力”——中國細(xì)胞生物學(xué)學(xué)會(huì)全體會(huì)員代表大會(huì)暨第十二次學(xué)術(shù)大會(huì)論文摘要集[C];2011年

5 ;HSP70 decreases receptor-dependent phosphorylation of Smad2 and blocks TGF-β-induced epithelial-mesenchymal transition[A];“細(xì)胞活動(dòng) 生命活力”——中國細(xì)胞生物學(xué)學(xué)會(huì)全體會(huì)員代表大會(huì)暨第十二次學(xué)術(shù)大會(huì)論文摘要集[C];2011年

6 ;Maternal Smad3 Deficiency Compromises Decidualization in Mice[A];“細(xì)胞活動(dòng) 生命活力”——中國細(xì)胞生物學(xué)學(xué)會(huì)全體會(huì)員代表大會(huì)暨第十二次學(xué)術(shù)大會(huì)論文摘要集[C];2011年

7 Jingmin Zhao;Jia Wang;Jun Yu;;Inhibitory role of Smad7 in hepatocarcinogenesis in mice and in vitro[A];中華醫(yī)學(xué)會(huì)第十六次全國病毒性肝炎及肝病學(xué)術(shù)會(huì)議論文匯編[C];2013年

8 Bensoussan D.;Stoltz J.F.;de Isla N;;Differentiation of human bone marrow mesenchymal stem cells induced by biaxial tension involves Smad3 activation[A];中國生理學(xué)會(huì)第23屆全國會(huì)員代表大會(huì)暨生理學(xué)學(xué)術(shù)大會(huì)論文摘要文集[C];2010年

9 ;Function of TGF-β/Smad4 Signaling in the Maintenance of Tissue Homeostasis[A];中國的遺傳學(xué)研究——遺傳學(xué)進(jìn)步推動(dòng)中國西部經(jīng)濟(jì)與社會(huì)發(fā)展——2011年中國遺傳學(xué)會(huì)大會(huì)論文摘要匯編[C];2011年

10 楊曉;;Targeted disruption of Smad4 in mouse epidemis results in failure of hair follicle cycling and formation of skin tumors[A];中國遺傳學(xué)會(huì)七屆一次青年研討會(huì)暨上海高校模式生物E——研究院第一屆模式生物學(xué)術(shù)研討會(huì)論文匯編[C];2005年

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2 張俊文;TGF-β信號(hào)通路中兩個(gè)與TβRI相互作用蛋白的功能研究[D];北京協(xié)和醫(yī)學(xué)院;2012年

3 胡祥鵬;復(fù)方芪參提取物調(diào)控TGF-β/Smad信號(hào)及miR-145、miR-21表達(dá)發(fā)揮抗肝纖維化—肝細(xì)胞癌作用[D];安徽醫(yī)科大學(xué);2015年

4 徐濤;NLRC5通過NF-κB與TGF-β1/Smad通路調(diào)控肝星狀細(xì)胞炎癥因子分泌和纖維化的功能及其機(jī)制研究[D];安徽醫(yī)科大學(xué);2015年

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6 黃闖;FTY-720調(diào)節(jié)去勢大鼠骨髓間充質(zhì)干細(xì)胞成骨分化Smad信號(hào)通路的機(jī)制研究[D];第四軍醫(yī)大學(xué);2015年

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8 田彥;三步序貫法對(duì)激素依賴型哮喘患者及激素撤減過程中氣道重塑模型大鼠TGF-β_1/Smad信號(hào)通路的影響[D];北京中醫(yī)藥大學(xué);2016年

9 計(jì)磊;突變體p53與生長轉(zhuǎn)化因子β信號(hào)在肺癌發(fā)生發(fā)展與轉(zhuǎn)移擴(kuò)散中的作用[D];華東師范大學(xué);2015年

10 牛立慢;TGF-β1/Smad3在四氯化碳誘導(dǎo)小鼠急性肝損傷中的表達(dá)及其作用研究[D];吉林大學(xué);2016年

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2 林琳;SnoN蛋白在RPE細(xì)胞TGF-β/Smad信號(hào)通路中的作用[D];福建醫(yī)科大學(xué);2015年

3 丁雪峰;芪藶強(qiáng)心提取物阻斷Smad3信號(hào)通路抑制血管緊張素Ⅱ誘導(dǎo)的心臟成纖維細(xì)胞轉(zhuǎn)分化的機(jī)制研究[D];川北醫(yī)學(xué)院;2015年

4 李祥亭;N-乙酰半胱氨酸對(duì)大鼠肺纖維化模型肺組織Smad家族基因表達(dá)的影響[D];遵義醫(yī)學(xué)院;2015年

5 李鑫靜;Smad4、Kindlin-2和Anxa2基因在胃癌組織中的表達(dá)及臨床病理意義[D];福建醫(yī)科大學(xué);2015年

6 汪呈;靶向Smurf1 HECT結(jié)構(gòu)域的小分子抑制劑的細(xì)胞學(xué)水平驗(yàn)證[D];石河子大學(xué);2015年

7 田茜華;補(bǔ)腎法、疏肝法對(duì)體外培養(yǎng)IVF-ET患者卵巢顆粒細(xì)胞中ACTA及其Smads信號(hào)通路的影響[D];河北醫(yī)科大學(xué);2015年

8 李春杰;新生大鼠高氧性肺損傷肺組織中Smad3及PPAR-γ的蛋白和mRNA表達(dá)及羅格列酮的干預(yù)作用[D];蘇州大學(xué);2015年

9 孫景英;CXCL9和Smad3的表達(dá)與新疆維吾爾族銀屑病發(fā)病關(guān)系的研究[D];石河子大學(xué);2015年

10 黃海平;MiR-145通過靶向作用于Smad3抑制鼻咽癌的侵襲和轉(zhuǎn)移能力[D];蘇州大學(xué);2015年

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