Pso P27抗原参与银屑病机制探索及清热凉血解毒法干预
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摘要
目的：Pso P27抗原是一种在银屑病患者鳞屑中提取的银屑病相关抗原,由肥大细胞产生,在银屑病皮损及外周血中以免疫复合物形式存在,与银屑病病情密切相关,药物治疗后皮损区抗原表达可显著下降,然而该抗原参与银屑病发病的确切机制尚不明确。
清热凉血解毒法治疗银屑病疗效确切,多项临床研究均支持了这一观点。而且在前期研究中,我们发现它能够有效降低Pso P27抗原在银屑病患者皮损中的表达。因此,为了揭示清热凉血解毒法治疗银屑病的分子生物学基础和科学内涵,为银屑病的临床治疗实践提供科学依据,本研究采用体外实验的方法,以探索Pso P27抗原诱发银屑病的内在机制,并且观察清热凉血解毒法体外干预效果。
内容：(1)pso p27抗原对银屑病相关免疫细胞T细胞、PBMC细胞的增殖及细胞因子分泌的影响,及此两种细胞上清液对Hacat细胞增殖的影响,以及清热凉血解毒含药血清对以上细胞增殖及细胞因子分泌的干预。
具体实验方法如下：培养银屑病患者T细胞、PBMC细胞及人永生化角质形成细胞株Hacat,用pso p27抗原进行干预,分别采用MTT、WST-1及WST-8的方法检测不同时点三种细胞的增殖度,并采用ELISA检测方法,检测T细胞及PBMC细胞因子分泌,包括IL-1、TFN-α。
采用大鼠含药血清制备的方法,制备清热凉血解毒含药血清(生地、紫草、土茯苓、白花蛇舌草、大青叶、赤芍、丹皮等),用不同浓度梯度含药血清干预T细胞、PBMC细胞及Hacat细胞,观察以上三种细胞的增殖情况(检测方法同前)。
(2)清热凉血解毒药物有效单体对Hacat细胞增殖及凋亡的影响。
选择该方药可能有效的四种单体：熊果酸(白花蛇舌草)、落新妇苷(土茯苓)、紫草素(紫草)及丹皮酚(牡丹皮),以不同浓度干预Hacat细胞,以明确药物单体对该细胞的干预作用。检测指标包括：细胞增殖(WST-8)、细胞周期,细胞凋亡(流式细胞仪技术及免疫荧光技术均采用AV/PI双染法),RT-PCR观察该四种单体对Hacat细胞促凋亡基因Bax及抑凋亡基因Bcl-xl的影响。
结果：(1)Pso P27抗原在体外并不能有效诱导T细胞的活化,同时对其细胞因子的分泌亦无明显影响,但是它在一定程度上可以促进PBMC细胞的体外增殖,诱导其TNF-α的分泌。同时,银屑病患者PBMC上清液以及Pso p27干预后PBMC匕清液均可以刺激Hacat细胞的体外增殖,且抗原干预后增殖效果更为明显。而清热凉血解毒含药血清则能够在一定程度上抑制T细胞、PBMC细胞以及Hacat细胞的体外增殖,其抑制作用与含药血清的浓度及剂量相关,只有当血清浓度达到20%时,其抑制作用才较为明显,且其中以大浓度及阳性对照组为最显著。与此同时,我们连续5日观察了含药血清对Hacat细胞增殖干预的影响中发现,其抑制效果与作用时间之间关系并不十分明确。
(2)中药单体对Hacat细胞的干预研究中,熊果酸、紫草素及丹皮酚均能够有效抑制Hacat细胞的体外增殖,且抑制作用与药物浓度密切相关,而落新妇苷则对Hacat细胞具有体外促增殖作用。在对Hacat细胞周期分布的影响中,前三者均可以对Hacat细胞产生周期阻滞,然而阻滞时期并不相同,如熊果酸可以将Hacat细胞阻滞于G1／G0期,而紫草素及丹皮酚则将Hacat细胞阻滞于G2／M期。由于落新妇苷对Hacat细胞具有促增殖作用,因此其对Hacat细胞的周期影响并不能用周期阻滞表示。它可以在一定程度上减少细胞G2/M期的含量,促使细胞及早进入G1／G0期。前三者还可以诱导Hacat细胞的凋亡,其凋亡率与正常对照组之间具有显著差异,而落新妇苷则可以抑制(?)Hacat细胞的早期凋亡,其早期凋亡率与对照组比较具有显著差异。在对Bcl-xl及Bax的干预作用中,四种单体干预效果均不同。熊果酸可以促进Bcl-xl的含量的升高,并降低Bax的含量,而紫草素则具有双抑制作用,丹皮酚则具有双促进作用,落新妇苷对它们的表达并无影响。
结论：
(1)Pso p27是银屑病相关抗原之一,多项研究表明它参与银屑病发病,然而具体机制尚不明确。
我们认为它与T细胞的活化及相关细胞因子的释放密切相关,然而实验结果证明它并不能有效诱导T细胞的体外增殖及细胞因子的释放,但却可以对PBMC细胞产生促增殖及促细胞因子释放的作用,同时还可以间接引起Hacat细胞的体外增殖。因此,我们认为Pso P27参与银屑病的发病与PBMC细胞密切相关,活化后的PBMC细胞可以释放相关细胞因子等,诱导银屑病的发病。然而,PBMC为淋巴细胞、单核细胞等组成的一个多细胞群,Pso P27抗原确切作用的靶细胞尚不完全明确,仍需要我们进一步通过实验,加以发现与验证。
(2)清热凉血解毒含药血清对银屑病发病相关细胞的干预存在不稳定性
清热凉血解毒含药血清对银屑病发病的多种细胞均具有体外抑制增殖的作用,其生物效应的发挥与药物浓度呈依赖关系。然而,由于中药含药血清的制备工艺较为繁琐,涉及环节较多,稳定性较差,因此我们应更加关注如何改进此中药药理学分析方法,使其能够更好地为中药复方的药理及药效研究服务。
此外,中药复方干预疾病多是多通路多靶位的,抑制相关细胞的体外增殖,仅仅是其作用机制的一个侧面,我们还需要全面认识清热凉血解毒含药血清疗效的发挥的作用机制。
(3)清热凉血解毒中药单体对Hacat细胞的增殖与凋亡作用各具特色
在本研究中我们检测了中药单体熊果酸、紫草素、丹皮酚及落新妇苷体外干预Hacat细胞,对其体外增殖、细胞周期分布、凋亡以及凋亡基因Bcl-xl与Bax表达的影响。
单体的药物作用既存在相同点,又各有特色。其中熊果酸、紫草素以及丹皮酚的作用,与白花蛇舌草、紫草以及丹皮在银屑病治疗中的作用效果基本保持一致,在体外实验中仍能够抑制Hacat细胞的增殖,同时促进其凋亡,但是对于凋亡基因Bax、Bcl的影响各不相同。
而落新妇苷在却能够体外促进Hacat细胞的增殖,并对其早期凋亡具有一定抑制能力,而对凋亡基因Bcl-xl及Bax的表达无影响。这与土茯苓治疗银屑病的临床疗效存在差异。我们考虑该单体可能并不是土茯苓治疗银屑病的有效单体,或者落新妇苷治疗银屑病的靶细胞并不是Hacat细胞而是T细胞等免疫细胞,或者与我们所选取的单体浓度相关。
Object
The psoriasis-associated antigen Pso p27, which was isolated from patients of psoriasis by Prof. Iverson, is shown to be a major antigen in the immune reactions in psoriasis lesions. It can be produced by mast cells and expressed in the skin lesions, and when the lesions are in remission, the expression of the antigen is reduced or omitted. What is more, Its immune complex can be detected in peripheral blood of psoriatic patients.
Traditional Chinese Medicine (TCM) made a great effect in treating psoriasis. And we have proved it can influence the expression of Pso P27. There was a suppression of Pso P27after treatment with TCM. So, we want to know the exactly mechanism of Pso p27participated in the pathogenesis of psoriasis and if the Pso p27play a crucial role in the mechanism of TCM in treating psoriasis in this study.
Content
The content can be divided into2parts.
(1)We detected the influence of pso p27antigen on the proliferation and the release of cytokines of psoriasis associated immunological cells (T cell and PBMC cell), and the proliferation of Hacat cells(a cell line of keratinocyte). And we made Qingre Liangxue Jiedu Decoction drug serum to observe the function of TCM on the above content. Here are the details of the experiments:we cultured T cells and PBMC cells which were separated from the psoriatic patients and Hacat cells. And then, we add pso p27in the culture medium of them for24h to detecte the proliferation of T cells and PBMC cells cells by WST-1and WST-8assay, and the release of cytokines by ELISA assy. What is more, we used the supernatant fluid of the T cells and PBMC cells to stimulate the Hacat cells and to see if there is a proliferation of Hacat cells. We made Qingre Liangxue Jiedu drug serum, and use different concentration to intervene on the T cells (including treated by pso p27), PBMC cells (including treated by pso p27) and Hacat cells.The assays just like which were mentioned.
(2)The influence of Traditional Chinese medicine monomers on the proliferation and apoptosis of Hacat cells We chose4kinds of Traditional Chinese medicine monomers:ursolic acid (Hedyotis diffusa), astilbin(Smilax glabra Roxb.), shikonin(Amebia euchroma Johnst), and Paeonol (Paeonia suffuticosa Andr). In this study, we want to know the exactly function of the monomers on Hacat cells. We tested the proliferation of Hacat cells by WST-8, and we observed the mitotic cycle and apoptosis rate of Hacat cells by flow cytometry and immunofluorescent microscope, what is more, we tested the expression of apoptosis gene Bcl-xl and Bax in Hacat cell by RT-PCR. All the cells were treated by different ratio of monomers.
Result
(1)Pso P27antigen cannot active T cells directly in vitro, it cannot stimulate the proliferation of T cells and have no effect on the release of correlative cytokines. But it can promote the proliferation of PBMC cells, and induce the release of TNF-a.When we add the supernatant fluid of PBMC cells it can promote the proliferation of Hacat cells. The Qingre Liangxue Jiedu drug serum can suppress the proliferation of T cells, PBMC cells and Hacat cells in vitro. The level of suppression related to the concentration of Qingre Liangxue Jiedu drug serum, when the ratio of the drug serum was added in the culture medium up to20%, it made an obviously suppression on Hacat cells, especially in the large dose group and the positive control group. At the meantime, we observed the proliferation of Hacat cells treated by drug serum for5days, but there was no clear relationship between the suppression of Hacat cells and the treated time.
(2) In the research of Traditional Chinese medicine monomers and Hacat cells. We found that ursolic acid,,shikonin and paeonol can inhibit the proliferation of Hacat cells, and the inhibition related closely to the content of monomers. However, astilbin can stimulate the proliferation of Hacat cells. Moreover, c, shikonin and paeonol can block the cell cycle, but there were some differences. For example, ursolic acid can increase G1/G0phase of cell cycle, meanwhile, shikonin and paeonol can increase G2/M phase. Because astilbin can promote the proliferation of Hacat cells, so when we analyze the cell cycle invented by it, although it can decrease G2/M phase and increase G1/G0phase, we can't regard this as cell cycle blocking. Maybe it just let more cells to go to next cell cycle. What is more, ursolic acid, shikonin and paeonol can induce the apoptosis of Hacat cells. The results showed that there was a significant statistical difference between the intervention groups and the control group in apoptosis rate. But astilbin can prevent Hacat cells from apoptosis, the significant statistical difference in early apoptosis rate between intervention groups and control group was detected too. In this reaseach, we also observed the influence of monomers on the expression of apoptosis gene of Hacat cells, such as Bcl-xl and Bax. Bcl-xl is one of apoptosis inhibiting gene and Bax is an apoptosis trigger gene, they have opposite effect on apoptosis of cells. The influence on the2genes was quite distinct among monomers. Ursolic acid can increase the expression of Bcl-x1and inhibit the expression of Bax of Hacat cells, but shikonin can inhibit the expression both of them, paeonol can increase the expression both of them. Meanwhile, Astilbin had no obvious effect on the expression of the2genes.
Conclusion
Pso p27, is the only antigen in psoriatic lesions recognized by antibodies from psoriatic scale, to our knowledge. The mechanism of it in participating psoriasis is going to be investigated. Lots of studies have showed that T cell-mediated keratinocyte proliferation plays a key pathogenetic role in psoriasis. What is more, we thought that Pso p27can activate T cells and induce the release of cytokine, which can mediate proliferation of keratinocyte. However, the results showed there were no activation and the release of cytokines of T cells, the pso p27just activated PBMC cells. So we still don't know the exact target cells and mechanism of pso p27made its role in psoriasis. We need some new hypothesizes and more experiments to inspect and verify.
Qingre Liangxue Jiedu drug serum can inhibit the proliferation of kinds of cells related to psoriasis, and the function had a close relation to the dose of drug serum. But the drug serum had a poor stability, because the manufacture craft was complex. So we should pay attention to improving the manufacture craft. What is more, the characters of Chinese herbal compound in treating psoriasis was multi-target and multi-access, inhibition of the proliferation of cells just was one aspect of its function, we should make a all-around understanding of the Qingre Liangxue Jiedu drug serum.
In this project, we also observed the function of Traditional Chinese medicine monomers on the proliferation, cell cycle, apoptosis, the expression of apoptosis genes Bcl-xl and Bax of Hacat cells in vitro. The function of these monomers had similarities, but there were still some differences. The influence on Hacat cells of ursolic acid, shikonin and paeonol was unanimous with the effect of Hedyotis diffusa, Arnebia euchroma Johnst and Paeonia suffuticosa Andrin in treating psoriasis, but astilbin can induce the proliferation of Hacat cells in vitro and prevent the apoptosis of Hacat cells, this was quite different with the effect of Smilax glabra Roxb in treating psoriasis in clinic, so we reasoned that the trigger-cell of in treating psoriasis is not karatinocye, or astilbin is not the pivotal monomer of Smilax glabra Roxb in treating psoriasis.
清热凉血解毒法治疗银屑病疗效确切,多项临床研究均支持了这一观点。而且在前期研究中,我们发现它能够有效降低Pso P27抗原在银屑病患者皮损中的表达。因此,为了揭示清热凉血解毒法治疗银屑病的分子生物学基础和科学内涵,为银屑病的临床治疗实践提供科学依据,本研究采用体外实验的方法,以探索Pso P27抗原诱发银屑病的内在机制,并且观察清热凉血解毒法体外干预效果。
内容：(1)pso p27抗原对银屑病相关免疫细胞T细胞、PBMC细胞的增殖及细胞因子分泌的影响,及此两种细胞上清液对Hacat细胞增殖的影响,以及清热凉血解毒含药血清对以上细胞增殖及细胞因子分泌的干预。
具体实验方法如下：培养银屑病患者T细胞、PBMC细胞及人永生化角质形成细胞株Hacat,用pso p27抗原进行干预,分别采用MTT、WST-1及WST-8的方法检测不同时点三种细胞的增殖度,并采用ELISA检测方法,检测T细胞及PBMC细胞因子分泌,包括IL-1、TFN-α。
采用大鼠含药血清制备的方法,制备清热凉血解毒含药血清(生地、紫草、土茯苓、白花蛇舌草、大青叶、赤芍、丹皮等),用不同浓度梯度含药血清干预T细胞、PBMC细胞及Hacat细胞,观察以上三种细胞的增殖情况(检测方法同前)。
(2)清热凉血解毒药物有效单体对Hacat细胞增殖及凋亡的影响。
选择该方药可能有效的四种单体：熊果酸(白花蛇舌草)、落新妇苷(土茯苓)、紫草素(紫草)及丹皮酚(牡丹皮),以不同浓度干预Hacat细胞,以明确药物单体对该细胞的干预作用。检测指标包括：细胞增殖(WST-8)、细胞周期,细胞凋亡(流式细胞仪技术及免疫荧光技术均采用AV/PI双染法),RT-PCR观察该四种单体对Hacat细胞促凋亡基因Bax及抑凋亡基因Bcl-xl的影响。
结果：(1)Pso P27抗原在体外并不能有效诱导T细胞的活化,同时对其细胞因子的分泌亦无明显影响,但是它在一定程度上可以促进PBMC细胞的体外增殖,诱导其TNF-α的分泌。同时,银屑病患者PBMC上清液以及Pso p27干预后PBMC匕清液均可以刺激Hacat细胞的体外增殖,且抗原干预后增殖效果更为明显。而清热凉血解毒含药血清则能够在一定程度上抑制T细胞、PBMC细胞以及Hacat细胞的体外增殖,其抑制作用与含药血清的浓度及剂量相关,只有当血清浓度达到20%时,其抑制作用才较为明显,且其中以大浓度及阳性对照组为最显著。与此同时,我们连续5日观察了含药血清对Hacat细胞增殖干预的影响中发现,其抑制效果与作用时间之间关系并不十分明确。
(2)中药单体对Hacat细胞的干预研究中,熊果酸、紫草素及丹皮酚均能够有效抑制Hacat细胞的体外增殖,且抑制作用与药物浓度密切相关,而落新妇苷则对Hacat细胞具有体外促增殖作用。在对Hacat细胞周期分布的影响中,前三者均可以对Hacat细胞产生周期阻滞,然而阻滞时期并不相同,如熊果酸可以将Hacat细胞阻滞于G1／G0期,而紫草素及丹皮酚则将Hacat细胞阻滞于G2／M期。由于落新妇苷对Hacat细胞具有促增殖作用,因此其对Hacat细胞的周期影响并不能用周期阻滞表示。它可以在一定程度上减少细胞G2/M期的含量,促使细胞及早进入G1／G0期。前三者还可以诱导Hacat细胞的凋亡,其凋亡率与正常对照组之间具有显著差异,而落新妇苷则可以抑制(?)Hacat细胞的早期凋亡,其早期凋亡率与对照组比较具有显著差异。在对Bcl-xl及Bax的干预作用中,四种单体干预效果均不同。熊果酸可以促进Bcl-xl的含量的升高,并降低Bax的含量,而紫草素则具有双抑制作用,丹皮酚则具有双促进作用,落新妇苷对它们的表达并无影响。
结论：
(1)Pso p27是银屑病相关抗原之一,多项研究表明它参与银屑病发病,然而具体机制尚不明确。
我们认为它与T细胞的活化及相关细胞因子的释放密切相关,然而实验结果证明它并不能有效诱导T细胞的体外增殖及细胞因子的释放,但却可以对PBMC细胞产生促增殖及促细胞因子释放的作用,同时还可以间接引起Hacat细胞的体外增殖。因此,我们认为Pso P27参与银屑病的发病与PBMC细胞密切相关,活化后的PBMC细胞可以释放相关细胞因子等,诱导银屑病的发病。然而,PBMC为淋巴细胞、单核细胞等组成的一个多细胞群,Pso P27抗原确切作用的靶细胞尚不完全明确,仍需要我们进一步通过实验,加以发现与验证。
(2)清热凉血解毒含药血清对银屑病发病相关细胞的干预存在不稳定性
清热凉血解毒含药血清对银屑病发病的多种细胞均具有体外抑制增殖的作用,其生物效应的发挥与药物浓度呈依赖关系。然而,由于中药含药血清的制备工艺较为繁琐,涉及环节较多,稳定性较差,因此我们应更加关注如何改进此中药药理学分析方法,使其能够更好地为中药复方的药理及药效研究服务。
此外,中药复方干预疾病多是多通路多靶位的,抑制相关细胞的体外增殖,仅仅是其作用机制的一个侧面,我们还需要全面认识清热凉血解毒含药血清疗效的发挥的作用机制。
(3)清热凉血解毒中药单体对Hacat细胞的增殖与凋亡作用各具特色
在本研究中我们检测了中药单体熊果酸、紫草素、丹皮酚及落新妇苷体外干预Hacat细胞,对其体外增殖、细胞周期分布、凋亡以及凋亡基因Bcl-xl与Bax表达的影响。
单体的药物作用既存在相同点,又各有特色。其中熊果酸、紫草素以及丹皮酚的作用,与白花蛇舌草、紫草以及丹皮在银屑病治疗中的作用效果基本保持一致,在体外实验中仍能够抑制Hacat细胞的增殖,同时促进其凋亡,但是对于凋亡基因Bax、Bcl的影响各不相同。
而落新妇苷在却能够体外促进Hacat细胞的增殖,并对其早期凋亡具有一定抑制能力,而对凋亡基因Bcl-xl及Bax的表达无影响。这与土茯苓治疗银屑病的临床疗效存在差异。我们考虑该单体可能并不是土茯苓治疗银屑病的有效单体,或者落新妇苷治疗银屑病的靶细胞并不是Hacat细胞而是T细胞等免疫细胞,或者与我们所选取的单体浓度相关。
Object
The psoriasis-associated antigen Pso p27, which was isolated from patients of psoriasis by Prof. Iverson, is shown to be a major antigen in the immune reactions in psoriasis lesions. It can be produced by mast cells and expressed in the skin lesions, and when the lesions are in remission, the expression of the antigen is reduced or omitted. What is more, Its immune complex can be detected in peripheral blood of psoriatic patients.
Traditional Chinese Medicine (TCM) made a great effect in treating psoriasis. And we have proved it can influence the expression of Pso P27. There was a suppression of Pso P27after treatment with TCM. So, we want to know the exactly mechanism of Pso p27participated in the pathogenesis of psoriasis and if the Pso p27play a crucial role in the mechanism of TCM in treating psoriasis in this study.
Content
The content can be divided into2parts.
(1)We detected the influence of pso p27antigen on the proliferation and the release of cytokines of psoriasis associated immunological cells (T cell and PBMC cell), and the proliferation of Hacat cells(a cell line of keratinocyte). And we made Qingre Liangxue Jiedu Decoction drug serum to observe the function of TCM on the above content. Here are the details of the experiments:we cultured T cells and PBMC cells which were separated from the psoriatic patients and Hacat cells. And then, we add pso p27in the culture medium of them for24h to detecte the proliferation of T cells and PBMC cells cells by WST-1and WST-8assay, and the release of cytokines by ELISA assy. What is more, we used the supernatant fluid of the T cells and PBMC cells to stimulate the Hacat cells and to see if there is a proliferation of Hacat cells. We made Qingre Liangxue Jiedu drug serum, and use different concentration to intervene on the T cells (including treated by pso p27), PBMC cells (including treated by pso p27) and Hacat cells.The assays just like which were mentioned.
(2)The influence of Traditional Chinese medicine monomers on the proliferation and apoptosis of Hacat cells We chose4kinds of Traditional Chinese medicine monomers:ursolic acid (Hedyotis diffusa), astilbin(Smilax glabra Roxb.), shikonin(Amebia euchroma Johnst), and Paeonol (Paeonia suffuticosa Andr). In this study, we want to know the exactly function of the monomers on Hacat cells. We tested the proliferation of Hacat cells by WST-8, and we observed the mitotic cycle and apoptosis rate of Hacat cells by flow cytometry and immunofluorescent microscope, what is more, we tested the expression of apoptosis gene Bcl-xl and Bax in Hacat cell by RT-PCR. All the cells were treated by different ratio of monomers.
Result
(1)Pso P27antigen cannot active T cells directly in vitro, it cannot stimulate the proliferation of T cells and have no effect on the release of correlative cytokines. But it can promote the proliferation of PBMC cells, and induce the release of TNF-a.When we add the supernatant fluid of PBMC cells it can promote the proliferation of Hacat cells. The Qingre Liangxue Jiedu drug serum can suppress the proliferation of T cells, PBMC cells and Hacat cells in vitro. The level of suppression related to the concentration of Qingre Liangxue Jiedu drug serum, when the ratio of the drug serum was added in the culture medium up to20%, it made an obviously suppression on Hacat cells, especially in the large dose group and the positive control group. At the meantime, we observed the proliferation of Hacat cells treated by drug serum for5days, but there was no clear relationship between the suppression of Hacat cells and the treated time.
(2) In the research of Traditional Chinese medicine monomers and Hacat cells. We found that ursolic acid,,shikonin and paeonol can inhibit the proliferation of Hacat cells, and the inhibition related closely to the content of monomers. However, astilbin can stimulate the proliferation of Hacat cells. Moreover, c, shikonin and paeonol can block the cell cycle, but there were some differences. For example, ursolic acid can increase G1/G0phase of cell cycle, meanwhile, shikonin and paeonol can increase G2/M phase. Because astilbin can promote the proliferation of Hacat cells, so when we analyze the cell cycle invented by it, although it can decrease G2/M phase and increase G1/G0phase, we can't regard this as cell cycle blocking. Maybe it just let more cells to go to next cell cycle. What is more, ursolic acid, shikonin and paeonol can induce the apoptosis of Hacat cells. The results showed that there was a significant statistical difference between the intervention groups and the control group in apoptosis rate. But astilbin can prevent Hacat cells from apoptosis, the significant statistical difference in early apoptosis rate between intervention groups and control group was detected too. In this reaseach, we also observed the influence of monomers on the expression of apoptosis gene of Hacat cells, such as Bcl-xl and Bax. Bcl-xl is one of apoptosis inhibiting gene and Bax is an apoptosis trigger gene, they have opposite effect on apoptosis of cells. The influence on the2genes was quite distinct among monomers. Ursolic acid can increase the expression of Bcl-x1and inhibit the expression of Bax of Hacat cells, but shikonin can inhibit the expression both of them, paeonol can increase the expression both of them. Meanwhile, Astilbin had no obvious effect on the expression of the2genes.
Conclusion
Pso p27, is the only antigen in psoriatic lesions recognized by antibodies from psoriatic scale, to our knowledge. The mechanism of it in participating psoriasis is going to be investigated. Lots of studies have showed that T cell-mediated keratinocyte proliferation plays a key pathogenetic role in psoriasis. What is more, we thought that Pso p27can activate T cells and induce the release of cytokine, which can mediate proliferation of keratinocyte. However, the results showed there were no activation and the release of cytokines of T cells, the pso p27just activated PBMC cells. So we still don't know the exact target cells and mechanism of pso p27made its role in psoriasis. We need some new hypothesizes and more experiments to inspect and verify.
Qingre Liangxue Jiedu drug serum can inhibit the proliferation of kinds of cells related to psoriasis, and the function had a close relation to the dose of drug serum. But the drug serum had a poor stability, because the manufacture craft was complex. So we should pay attention to improving the manufacture craft. What is more, the characters of Chinese herbal compound in treating psoriasis was multi-target and multi-access, inhibition of the proliferation of cells just was one aspect of its function, we should make a all-around understanding of the Qingre Liangxue Jiedu drug serum.
In this project, we also observed the function of Traditional Chinese medicine monomers on the proliferation, cell cycle, apoptosis, the expression of apoptosis genes Bcl-xl and Bax of Hacat cells in vitro. The function of these monomers had similarities, but there were still some differences. The influence on Hacat cells of ursolic acid, shikonin and paeonol was unanimous with the effect of Hedyotis diffusa, Arnebia euchroma Johnst and Paeonia suffuticosa Andrin in treating psoriasis, but astilbin can induce the proliferation of Hacat cells in vitro and prevent the apoptosis of Hacat cells, this was quite different with the effect of Smilax glabra Roxb in treating psoriasis in clinic, so we reasoned that the trigger-cell of in treating psoriasis is not karatinocye, or astilbin is not the pivotal monomer of Smilax glabra Roxb in treating psoriasis.
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