In Vivo Protein Transduction: Delivery of PEP-1-SOD1 Fusion Protein into Myocardium Efficiently Protects against Ischemic Insult
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- Molecules and Cells
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- v.27 no.2
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- pp.159-166
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- 2009
Myocardial ischemia-reperfusion injury is a medical problem occurring as damage to the myocardium following blood flow restoration after a critical period of coronary occlusion. Oxygen free radicals (OFR) are implicated in reperfusion injury after myocardial ischemia. The antioxidant enzyme, Cu, Zn-superoxide dismutase (Cu, Zn-SOD, also called SOD1) is one of the major means by which cells counteract the deleterious effects of OFR after ischemia. Recently, we reported that a PEP-1-SOD1 fusion protein was efficiently delivered into cultured cells and isolated rat hearts with ischemia-reperfusion injury. In the present study, we investigated the protective effects of the PEP-1-SOD1 fusion protein after ischemic insult. Immunofluorescecnce analysis revealed that the expressed and purified PEP-1-SOD1 fusion protein injected into rat tail veins was efficiently transduced into the myocardium with its native protein structure intact. When injected into Sprague-Dawley rat tail veins, the PEP-1-SOD1 fusion protein significantly attenuated myocardial ischemia-reperfusion damage; characterized by improving cardiac function of the left ventricle, decreasing infarct size, reducing the level of malondialdehyde (MDA), decreasing the release of creatine kinase (CK) and lactate dehydrogenase (LDH), and relieving cardiomyocyte apoptosis. These results suggest that the biologically active intact forms of PEP-1-SOD1 fusion protein will provide an efficient strategy for therapeutic delivery in various diseases related to SOD1 or to OFR.
1. The 'Kao Zheng Pai(考證派) comes from the 'Zhe Zhong Pai' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金娥), Yoshida Koton(吉田篁墩) became central members, and the rise of the methodology of historical research(考證學) influenced the members of the 'Zhe Zhong Pai', and the trend of historical research changed from confucianism to medicine, making a school of medicine based on the study of texts and proving that the classics were right. 2. Based on the function of 'Nei Qu Li '(內驅力) the 'Kao Zheng Pai', in the spirit of 'use confucianism as the base', researched letters, meanings and historical origins. Because they were influenced by the methodology of historical research(考證學) of the Qing era, they valued the evidential research of classic texts, and there was even one branch that did only historical research, the 'Rue Xue Kao Zheng Pai'(儒學考證派). Also, the 'Yi Xue Kao Zheng Pai'(醫學考證派) appeared by the influence of Yoshida Kouton and Kariya Ekisai(狩谷掖齋). 3. In the 'Kao Zheng Pai(考證派)'s theories and views the 'Yi Xue Kao Zheng Pai' did not look at medical scriptures like the "Huang Di Nei Jing"("黃帝內經") and did not do research on 'medical' related areas like acupuncture, the meridian and medicinal herbs. Since they were doctors that used medicine, they naturally were based on 'formulas'(方劑) and since their thoughts were based on the historical ideologies, they valued the "Shang Han Ja Bing Lun" which was revered as the 'ancestor of all formulas'(衆方之祖). 4. The lives of the important doctors of the 'Kao Zheng Pai' Meguro Dotaku(目黑道琢) Yamada Seichin(山田正珍), Yamada Kyoko(山田業廣), Mori Ritsi(森立之) Kitamura Naohara(喜多村直寬) are as follows. 1) Meguro Dotaku(目黑道琢 1739
1.The 'Kao Zheng Pai'(考證派) comes from the 'Zhe Zhong Pai(折衷派)' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金峨), Yoshida Koton(古田篁墩
The purpose of this paper is to explore Confucian Philosophy of the Chèn-wěi books in the Han dynasty, and to find the social and political implications that it reveals. The study is needed because the Chèn-wěi books contain ideas for solving the problems of the times. And topics that are lacking or not sufficient in scripture are discussed in more depth. As a result of this study, the Confucian Philosophy of the Chèn-wěi books was discovered to have the following characteristics: The Chèn-wěi books were a mixture of those who wanted to deny the legitimacy of the Han dynasty and those who wanted to defend it. The forces that tried to deny it went in the direction of denying the legitimacy of the Liú-Han regime and defending the emergence of new forces by pursuing the theory of sensation between heaven and man (天人感應說) since Dong Zhong-Shu and insisting on 'the theory of Hán-Wēn (寒溫說: Hán-Wēn-Shuō). They also laid the theoretical foundation for a new force to emerge through Qì-monolithic cosmology. But this is a natural consequence of the incompetence, deviation, and the various Zāiyì of the West-Han regime at the time. However, those who wanted to defend the legitimacy of the Han dynasty wanted to meet the political needs of the emperor and the vested interests around the emperor as well as the legitimacy of the Liú-Han regime through Shòu-Mìng-Zhī-Fú (受命之符), the Dào and Qì dualistic cosmology, the theory of Guà-Qì (卦氣說: Guà-Qì-Shuō) and other means. Because Shòu-Mìng-Zhī-Fú defended the legitimacy of the Hàn dynasty by mystifying Gāo-Zŭ of Hàn Liú-Bāng's teacher, Zhāng-Liáng (張良). Also because the Dào and Qì dualistic cosmology was strengthening the order of the feudal class as Cosmogony by subdividing its creation process from the substance of a metaphysical's Tài-Yì (太易) to the matter of a physical's Tài-Chū (太初), Tài-Shǐ (太始) and Tài-Sù (太素). And it is because the theory of Guà-Qì was more active in meeting the political demands of the then ruling circles by connecting nature and personnel more closely by mystifying it, than that of the existing Mèng-Xǐ and Jīng-Fáng. In view of this, the Chèn-wěi books, except for the theory of Hán-Wēn and the Qì-monolithic cosmology designed to quickly end the harsh environment of the end of the West-Han dynasty, served as a champion of the Liú-Han regime and its vested interests. The Confucian Philosophy of the Chen-wěi books can be assessed as having a strong political inclination. Because the theory of Chèn-wěi was formed due to the need to pursue the characteristic of arbitrary interpretation of New-Text Scholarship in an extreme manner and respond more actively to the socio-political needs of the ruling.