マグネシウム投与によるシスプラチン起因性腎障害の予防効果およびその機序の解明

阐明镁给药对顺铂所致肾损伤的预防作用及其机制

• 批准号: 15H00484
• 负责人: 齋藤 佳敬
• 金额: $ 0.38万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Scientists
• 财政年份: 2015
• 资助国家: 日本
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15H00484/
• 关键词: シスプラチン; マグネシウム; トランスポータ

本研究ではラットを用いて、CDDP腎障害に対するマグネシウム(Mg)投与の予防・軽減効果の検証およびその機序の検討を行った。シスプラチン(CDDP)2.5mg/kg/週の腹腔内投与を3回繰り返すことにより、CDDPの反復投与を再現した。採血はCDDP投与前、CDDP投与5日後、7日後に行った。その結果、腎機能障害の指標として用いた血清クレアチニン値はCDDP1回目投与5日後より生理食塩水を投与したコントロールラットと比較して有意に上昇し、その後もコントロール郡では継時的に上昇したが、Mg併用によりその上昇は有意に抑制された。血清Mg値はCDDP1回目投与後より有意に低下し、その後は横ばいで推移したが、こちらもMgを併用することにより有意にその低下は抑制された。CDDPの近位尿細管への取り込みを担うOrganic cation transporter 2(rOct2)の発現量はCDDP単回投与により、コントロールラットと比較して約1.4倍に増加したが、CDDPをMgと併用投与した場合、その発現量は約0.5倍へと低下した。近位尿細管からのCDDP排出を担うMultidrug and toxin extrusion protein l(rMATE1)の発現量はCDDP単回投与では変動が認められなかったが、CDDPとMgの併用時には1.4倍増加した。その結果、CDDP-Mg併用投与群ではCDDP単回投与後の腎臓内プラチナ蓄積量はCDDP単独投与群と比較して有意に低下した。しかし、CDDP投与2回目ではMgの併用の有無によらず両トランスポータの発現変動は同等であり、さらに腎臓内プラチナ蓄積量にも差はみられなかった。これらの結果からMgによる腎保護効果はCDDPの腎臓内動態に関与するトランスポータに作用する間接的効果ならびに抗酸化作用などの直接的効果が協働している可能性が示唆された(論文投稿中)。今後はCDDP投与3回目におけるトランスポータ発現変動および腎臓内プラチナ蓄積に関する検討を行う。また、腎由来細胞および腎上皮細胞膜ベジクルを用いたこれらトランスポータの機能解析、ならびに抗酸化作用など他の機序の可能性の評価を実施する予定である。

The purpose of this study is to evaluate the effectiveness of the prevention strategy (Mg). The results show that there are significant differences between the two groups in this study. in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows: in this study, the results of this study are as follows. Patients received intraperitoneal injection (CDDP) 2.5mg/kg/ for 3 times and returned to the abdominal cavity for 3 times, CDDP injection and recurrence therapy. The blood CDDP was given before, and the CDDP was given 5 days and 7 days later. According to the results of the test, the failure of the machine means that the CDDP1 is returned to the eye after 5 days, and after 5 days, the physiological water is thrown back to the eye. the results are as follows: the results of the test, the failure of the machine means that you can use the serum to return to the eye and 5 days later, the physiological water is injected and the food is used to restrain the health of the health care station. The serum Mg CDDP1 was returned to the eye and then was intentionally lowered, and the Mg was suppressed intentionally. CDDP proximal urine tube was used to determine the dose of Organic cation transporter 2 (rOct2). The dose of CDDP was about 1. 4 times higher than that of CDDP, and the dose of CDDP was 1. 4 times higher than that of placebo. The proximal urethral tube was used to measure the excretion of Multidrug and toxin extrusion protein l (rMATE1), the amount of CDDP was returned to the urine, and the Mg of CDDP was 1.4 times longer than that of the control. The results of the experiment, the CDDP-Mg investment and the group investment CDDP the return investment and the later, the CDDP investment was significantly lower than that of the group investment. You can find the same amount of money in the same amount of money as in the same amount of money, and the amount of money you need to invest in the same amount of money, the amount of money you need to pay for the same amount of money, the amount of money you need to pay for the same amount of money, the amount of money you need to pay for the same amount of money, the amount of money you need to buy, and the amount of money you need to pay for it. The results show that the effects of Mg and anti-acidizing effects on the dynamics of the CDDP system and the anti-acidizing effect directly indicate that the possibility of the anti-acidizing effect is significant (in the article contribution). In the future, CDDP will invest in the following three times. You will see that you will be able to pay for your business in the future. The reason for this is that the membrane of epithelial cells can be analyzed by means of anti-acidification mechanism, the possibility of anti-acidizing and the possibility of predetermination.