JP2004144767A - Method of judging vaginal secretion or cervical mucus of urgent premature delivery pregnant woman - Google Patents
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Abstract
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本発明は、早産の検出に有用な、切迫早産妊婦の膣分泌液又は頸管粘液の鑑別法に関する。 The present invention relates to a method for identifying vaginal secretion or cervical mucus of an imminently premature pregnant woman, which is useful for detecting premature labor.
妊娠に伴う異常として早産があり、その原因は多岐にわたるが、主に上行感染、子宮内感染、絨毛羊膜炎や胎盤早期剥離とされている。
感染症や絨毛羊膜炎が原因の場合、母体血液中の血中Ｃ反応性蛋白（ＣＲＰ）濃度や、白血球数が増加するため、これらを測定することにより、早産の検査が実施されている。
Premature birth is an abnormality associated with pregnancy, and its causes vary widely, but are mainly described as ascending infection, intrauterine infection, chorioamnionitis and early placental detachment.
In the case of infection or chorioamnionitis, the blood C-reactive protein (CRP) concentration in maternal blood and the number of white blood cells increase, and premature birth tests are performed by measuring these.
しかしながら、ＣＲＰ濃度や白血球数は血液由来であるため、早産以外の別の因子によっても上昇してしまい、早産にのみ特異的なものとは言い難かった。またＣＲＰは血液中に微量にしか検出されず、測定の感度は低いという問題もあった。このように、血液中のＣＲＰ濃度や白血球数を測定し、早期に早産を診断することは困難であった。 However, CRP concentration and leukocyte count are derived from blood, so they were increased by other factors other than premature birth, and it was hard to say that they were specific only to premature birth. In addition, CRP is detected only in a trace amount in blood, and there is a problem that the sensitivity of the measurement is low. As described above, it was difficult to diagnose premature labor at an early stage by measuring the CRP concentration and white blood cell count in blood.
これに対し、最近、血液中のインターロイキン−６（ＩＬ−６）を測定することにより流早産を診断する方法が報告されている（特許文献１）。しかしながら、この方法においても、検体が母体血液であるため、感度や特異性などの点で充分満足できるものではなかった。
従って、本発明の目的は、早産の指標となる物質を検索し、その鑑別法を確立することにある。 Accordingly, an object of the present invention is to search for a substance that is an indicator of premature birth and establish a method for identifying the substance.
斯かる実状に鑑み、本発明者らは鋭意研究を行った結果、膣分泌液又は頸管粘液中のサイトカイン濃度上昇が、切迫早産妊婦に特異的であり、このサイトカイン量を測定すれば、切迫早産妊婦の膣分泌液等を鑑別できることを見出し、本発明を完成した。
すなわち、本発明は、切迫早産のトコライシス治療の前後において妊婦の膣分泌液中のインターロイキン−８濃度を測定し、比較することを特徴とする、切迫早産妊婦のトコライシス治療の効果を判定する方法を提供するものである。
In view of such circumstances, the present inventors have conducted intensive studies and as a result, the increase in cytokine concentration in vaginal fluid or cervical mucus is specific to imminent preterm birth pregnant women. The present inventors have found that vaginal secretions and the like of pregnant women can be distinguished, and completed the present invention.
That is, the present invention measures the interleukin-8 concentration in the vaginal secretion of a pregnant woman before and after tocolysis treatment for premature labor, and compares the method. Is provided.
本発明によれば、切迫早産妊婦の膣分泌液又は頸管粘液を感度良く鑑別することができ、早産の検出や診断、治療などに有用である。 According to the present invention, vaginal secretion or cervical mucus of an imminent premature delivery woman can be distinguished with high sensitivity, and is useful for detection, diagnosis, treatment, etc. of premature delivery.
本発明において使用する検体は、膣分泌液又は頸管粘液のいずれであってもよい。これらを採取する方法としては、膣や子宮頸管等にダメージを与えないように採取できる方法であれば特に制限されず、例えば注射筒の先にシリコンチューブ等のチューブや注射針などをつけ、これらを膣に挿入して採取する方法；注射筒自体を膣に挿入して採取する方法；後膣部円蓋に綿棒等の吸収材を挿入し、これに頸管粘液等を吸収させる方法などが挙げられる。これらのうち、綿棒を用いる方法が簡便であり好ましく、特にダクロン綿棒を用いると、抽出効率も良くなりより好ましい。綿棒を用いて検体を採取する場合には、まず綿球等で膣内の不純物を取り除き、膣鏡で確認しながら行うのが好ましい。 検 体 The specimen used in the present invention may be either vaginal fluid or cervical mucus. The method for collecting these is not particularly limited as long as it can be collected so as not to damage the vagina or the cervix, for example, by attaching a tube such as a silicon tube or an injection needle to the tip of a syringe, and A method of inserting the syringe into the vagina to collect it; a method of inserting the syringe itself into the vagina to collect it; a method of inserting an absorbent material such as a cotton swab into the posterior vaginal fornix to absorb cervical mucus, etc. Can be Among them, a method using a cotton swab is preferred because it is simple and convenient. In particular, when a Dacron cotton swab is used, the extraction efficiency is improved and it is more preferable. When a specimen is collected using a cotton swab, it is preferable to first remove impurities in the vagina with a cotton ball or the like, and then carry out confirmation with a colposcopy.
このようにして採取した検体は、そのまま測定に用いることもできるが、膣分泌液や頸管粘液の原液は粘性が非常に高く、ゾル状であったり、クロット化している場合が多いので、これらを希釈又は抽出して用いるのが好ましい。希釈又は抽出には、pH６〜８の緩衝液を用いるのが好ましく、例えばリン酸緩衝液、トリス緩衝液、グット緩衝液などが挙げられ、緩衝液のpHはpH７．２〜７．８の範囲であるのがより好ましい。 The specimens collected in this way can be used for measurement as they are, but vaginal secretions and undiluted solutions of cervical mucus are very viscous and often sol-like or clotted. It is preferable to use it after dilution or extraction. For dilution or extraction, it is preferable to use a buffer having a pH of 6 to 8, and examples thereof include a phosphate buffer, a Tris buffer, and a Good's buffer, and the pH of the buffer is in a range of pH 7.2 to 7.8. Is more preferable.
これらの緩衝液を用いて検体を希釈又は抽出するには、例えば注射筒を用いて検体を採取した場合には、検体を裁断するようにつぶし、これと緩衝液を混合することにより、ゾル状又はクロット状の検体中のサイトカインを緩衝液中に抽出するのが好ましい。この場合、用いる緩衝液は、検体の約５倍量以上であるのが、充分な抽出を行うために好ましい。
また、綿棒を用いて検体を採取した場合には、検体を吸収させた綿棒を緩衝液に浸し、この綿棒で緩衝液を攪拌することによって、緩衝液中に検体を抽出するのが好ましい。
In order to dilute or extract a sample using these buffers, for example, when a sample is collected using a syringe, the sample is crushed so as to be cut, and the buffer and the buffer are mixed to form a sol. Alternatively, it is preferable to extract cytokines in a clot-like specimen into a buffer. In this case, the amount of the buffer used is preferably at least about 5 times the amount of the sample in order to perform sufficient extraction.
When a specimen is collected using a cotton swab, it is preferable to extract the specimen into the buffer by immersing the cotton swab having absorbed the specimen in a buffer solution and stirring the buffer solution with the cotton swab.
膣分泌液又は頸管粘液中のサイトカイン量を測定する方法としては、バイオアッセイ法、免疫学的測定法など、サイトカイン量を測定できる方法であれば、公知の方法のいずれでもよいが、特に免疫学的に定量する方法を用いるのが好ましい。なお、ここで測定するサイトカインとしては、インターロイキン−６（ＩＬ−６）、インターロイキン−８（ＩＬ−８）、インターロイキン−１（ＩＬ−１）等が挙げられ、これらの１種又は２種以上を測定することにより、切迫早産妊婦の膣分泌液等を鑑別することができる。これらのサイトカインのうち、特にＩＬ−６、ＩＬ−８を測定するのが好ましい。 As a method for measuring the amount of cytokines in vaginal secretion fluid or cervical mucus, any known method may be used as long as the method can measure the amount of cytokines, such as a bioassay and an immunological assay. It is preferable to use a method for quantitative determination. The cytokines measured here include interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 (IL-1), and the like. By measuring the species or more, vaginal secretions and the like of a prematurely pregnant woman can be identified. Among these cytokines, it is particularly preferable to measure IL-6 and IL-8.
例えば、検体中のＩＬ−６をＥＬＩＳＡ法で測定するには、通常の方法に従って行えばよく、例えば９６穴のマイクロタイタープレートに第一抗体すなわちＩＬ−６に特異的なモノクローナル、又はポリクローナル抗体を感作したものを固相とし、これと検体を反応させることによって、固相上の抗体と検体中のＩＬ−６を結合させる。次いで洗浄操作によって未反応の蛋白を除去した後、第二抗体、すなわちＩＬ−６に特異的な酵素標識モノクローナル、又はポリクローナル抗体を反応させて、ＩＬ−６を介した抗原抗体反応によるサンドウィッチを形成させる。余剰の第二抗体を洗浄によって除去した後、第二抗体の標識酵素に対する基質溶液を加えて発色させ、停止液で酵素反応を停止させる。そして吸光度を吸光度計により測定し、標準品の検量線から試料中のＩＬ−６濃度を換算すればよい。 For example, in order to measure IL-6 in a sample by an ELISA method, a conventional method may be used. For example, a first antibody, that is, a monoclonal or polyclonal antibody specific to IL-6 is applied to a 96-well microtiter plate. The sensitized product is used as a solid phase, and the sample is reacted with the solid to bind the antibody on the solid phase to IL-6 in the sample. Then, after removing unreacted proteins by a washing operation, a second antibody, that is, an enzyme-labeled monoclonal or polyclonal antibody specific to IL-6 is reacted to form a sandwich by an antigen-antibody reaction mediated by IL-6. Let it. After removing the excess second antibody by washing, a substrate solution for the labeling enzyme of the second antibody is added to develop color, and the enzyme reaction is stopped with a stop solution. Then, the absorbance may be measured with an absorbance meter, and the IL-6 concentration in the sample may be converted from the calibration curve of the standard product.
また、インターロイキン−８（ＩＬ−８）及び他のサイトカインについてもＩＬ−６の測定法と同様にして測定することができる。また、市販のＩＬ−６、ＩＬ−８濃度測定用のサンドウィッチＥＬＩＳＡキットなどを用いることもできる。 イ ン タ ー In addition, interleukin-8 (IL-8) and other cytokines can be measured in the same manner as in the method for measuring IL-6. A commercially available sandwich ELISA kit for measuring IL-6 and IL-8 concentrations can also be used.
このようにして測定したサイトカイン量により切迫早産妊婦の膣分泌液又は頸管粘液を鑑別することができ、具体的には、正常妊婦のサイトカイン量と対比して、高い値を示したものを切迫早産妊婦の膣分泌液等であるとすることができる。
このように、妊婦の膣分泌液又は頸管粘液中のサイトカインを測定することで、正常妊婦と切迫早産妊婦の鑑別ができる。
The vaginal secretion or cervical mucus of the premature labor of premature birth can be distinguished by the amount of cytokine measured in this way. It can be a vaginal secretion of a pregnant woman or the like.
Thus, by measuring the cytokine in the vaginal fluid or cervical mucus of a pregnant woman, it is possible to distinguish a normal pregnant woman from an imminent prematurely delivered pregnant woman.
以下、実施例を挙げて本発明を更に詳細に説明するが、本発明はこれらに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.
実施例１
妊娠週齢の異なる正常妊婦８例、切迫早産と診断された妊婦８例の膣分泌液中のＩＬ−６、ＩＬ−８量及び血清中のＣＲＰ濃度と血液中の白血球数を下記の如く測定した。これらの結果を表１、表２、図１及び図２に示す。
Example 1
The amount of IL-6 and IL-8 in vaginal secretions, the CRP concentration in serum, and the number of leukocytes in blood were measured as follows in eight normal pregnant women with different gestational ages and eight pregnant women diagnosed with imminent premature labor. did. The results are shown in Table 1, Table 2, FIG. 1 and FIG.
検体採取法：
妊婦の後膣部円蓋にダクロン綿棒を挿入し、１０秒間程度綿棒を回転しながら膣分泌液を吸収させ、これを１mlの抽出液（５０mM ２−アミノ−２−ヒドロキシメチル−１，３−プロパンジオール、１％ ＢＳＡ、０．８９％ 塩化ナトリウム、０．２％ エチレンジアミン四酢酸二ナトリウム、１μｌ／ml アプロチニン、１μｌ／ml ジメチルスルホキシド、０．１７mg／ml フェニルメチルスルホニルフルオライド、１μｌ／ml ポリオキシエチレノクチルフェニルエーテル、０．５mg／ml アジ化ナトリウム；pH７．５）に浸し、ダクロン綿棒で抽出液を攪拌することによって、ダクロン綿棒に吸収された膣分泌液を抽出した。これを試料とした。尚、必要に応じて、抽出液で希釈して用いた。
Sample collection method:
Insert a dacron swab into the vaginal fornix of the pregnant woman, rotate the swab for about 10 seconds to absorb vaginal secretions, and add 1 ml of the extract (50 mM 2-amino-2-hydroxymethyl-1,3- Propanediol, 1% BSA, 0.89% sodium chloride, 0.2% disodium ethylenediaminetetraacetate, 1 μl / ml aprotinin, 1 μl / ml dimethyl sulfoxide, 0.17 mg / ml phenylmethylsulfonyl fluoride, 1 μl / ml poly The vaginal secretion absorbed by the Dacron swab was extracted by immersion in oxyethylenoctyl phenyl ether, 0.5 mg / ml sodium azide; pH 7.5) and stirring the extract with a Dacron swab. This was used as a sample. In addition, it diluted and used with the extract as needed.
ＩＬ−６測定法：
Ｒ＆Ｄ社Ｑｕａｎｔｉｋｉｎｅの測定方法に従って、以下のように膣分泌液中のＩＬ−６を測定した。すなわち、まずマウス抗ＩＬ−６モノクローナル抗体を感作してあるマイクロタイタープレートの各ウェルに１００μｌずつアッセイ希釈液を分注した後に、試料を１００μｌずつ加えた。次いで室温で２時間静置反応させた後、洗浄液各ウェル４００μｌずつで３回洗浄した。洗浄液を除去後、ホースラディッシュペルオキシダーゼ（ＨＲＰ）標識抗ＩＬ−６ポリクローナル抗体溶液を各ウェルに２００μｌずつ加え、室温で２時間静置反応させた。洗浄液４００μｌずつで３回洗浄後、テトラメチルベンチジンを基質とした発色溶液を各ウェル２００μｌずつ加え、室温で２０分間静置反応させた後、２Ｎの硫酸を停止液として各ウェルに５０μｌずつ加えて酵素反応を停止した。マイクロタイタープレートリーダーの測定波長を４５０nmと５５０nmの２波長に設定し、吸光度を測定した。試料中のＩＬ−６濃度は、標準品の検量線から換算した。
IL-6 measurement method:
According to the measurement method of R & D Quantikine, IL-6 in vaginal secretion was measured as follows. That is, first, 100 μl of an assay diluent was dispensed into each well of a microtiter plate sensitized with a mouse anti-IL-6 monoclonal antibody, and then 100 μl of a sample was added. Then, the reaction was allowed to stand at room temperature for 2 hours, followed by washing three times with 400 μl of each well of a washing solution. After removing the washing solution, 200 μl of a horseradish peroxidase (HRP) -labeled anti-IL-6 polyclonal antibody solution was added to each well, and the mixture was allowed to stand still at room temperature for 2 hours. After washing three times with 400 μl of a washing solution, 200 μl of a coloring solution using tetramethylbenzidine as a substrate was added to each well, and allowed to stand at room temperature for 20 minutes. After that, 50 μl of 2N sulfuric acid was added as a stop solution to each well. To stop the enzymatic reaction. The measurement wavelength of the microtiter plate reader was set to two wavelengths of 450 nm and 550 nm, and the absorbance was measured. The concentration of IL-6 in the sample was converted from the calibration curve of a standard product.
ＩＬ−８測定法：
Ｒ＆Ｄ社Ｑｕａｎｔｉｋｉｎｅの測定方法に従って、以下のように膣分泌液中のＩＬ−８を測定した。すなわち、まずマウス抗ＩＬ−８モノクローナル抗体を感作してあるマイクロタイタープレートの各ウェルに１００μｌずつアッセイ希釈液を分注した後に、試料を１００μｌずつ加えた。次いで室温で２時間静置反応させた後、洗浄液各ウェル４００μｌずつで３回洗浄した。洗浄液を除去後、ホースラディッシュペルオキシダーゼ（ＨＲＰ）標識抗ＩＬ−８ポリクローナル抗体溶液を各ウェルに２００μｌずつ加え、室温で２時間静置反応させた。洗浄液４００μｌずつで３回洗浄後、テトラメチルベンチジンを基質とした発色溶液を各ウェル２００μｌずつ加え、室温で２０分間静置反応させた後、２Ｎの硫酸を停止液として各ウェルに５０μｌずつ加えて酵素反応を停止した。マイクロタイタープレートリーダーの測定波長を４５０nmと５５０nmの２波長に設定し、吸光度を測定した。試料中のＩＬ−８濃度は、標準品の検量線から換算した。
IL-8 measurement method:
According to the measurement method of R & D Quantikine, IL-8 in vaginal secretion was measured as follows. That is, first, 100 μl of an assay diluent was dispensed into each well of a microtiter plate sensitized with a mouse anti-IL-8 monoclonal antibody, and then 100 μl of a sample was added. Then, the reaction was allowed to stand at room temperature for 2 hours, followed by washing three times with 400 μl of each well of a washing solution. After removing the washing solution, a horseradish peroxidase (HRP) -labeled anti-IL-8 polyclonal antibody solution was added to each well in an amount of 200 μl, and allowed to stand still at room temperature for 2 hours. After washing three times with 400 μl of a washing solution, 200 μl of a coloring solution using tetramethylbenzidine as a substrate was added to each well, and allowed to stand at room temperature for 20 minutes. After that, 50 μl of 2N sulfuric acid was added as a stop solution to each well. To stop the enzymatic reaction. The measurement wavelength of the microtiter plate reader was set to two wavelengths of 450 nm and 550 nm, and the absorbance was measured. The concentration of IL-8 in the sample was calculated from a calibration curve of a standard product.
一方、ＣＲＰ濃度は、妊婦の血清を試料として市販のキット（ヤトロン社製、ラテックス凝集法）で測定した。白血球数は、妊婦血液を用いてシスメックス社製自動血球計算機で測定した。 On the other hand, the CRP concentration was measured using a commercially available kit (manufactured by Yatron, latex agglutination method) using serum of a pregnant woman as a sample. The leukocyte count was measured by using an automatic hemocytometer manufactured by Sysmex Corporation using blood from pregnant women.
以上の結果から、ＩＬ−６の膣分泌液中濃度は、正常妊婦の場合、８例中６例が測定検出限界（０．０３ng／ml）以下であるが、切迫早産群では０．４２〜１３．０ng／mlとＭａｎｎ−Ｗｈｉｔｅｎｅｙ検定で有意（ｐ＜０．００１）に高値を示し、膣分泌液中のＩＬ−６量を測定することで切迫早産妊婦の膣分泌液を鑑別することができ、早産の検出が可能であることが判る（表１、表２、図１）。
また、ＩＬ−８の膣分泌液中濃度は、正常妊婦の場合１．５〜１２．１ng／mlであるが、切迫早産群では４１．５〜１６８０ng／mlとＭａｎｎ−Ｗｈｉｔｅｎｅｙ検定で有意（ｐ＜０．００１）に高値を示し、膣分泌液中のＩＬ−８量を測定することで切迫早産妊婦の膣分泌液を鑑別することができ、早産の検出が可能であることが判る。（表１、表２、図２）。
From the above results, the vaginal secretion level of IL-6 was lower than the detection limit (0.03 ng / ml) in 6 of 8 cases in normal pregnant women, but was 0.42 to 2 in the threatened premature birth group. The value of 13.0 ng / ml was significantly (p <0.001) high in the Mann-Whiteney test, and the amount of IL-6 in the vaginal secretion was measured. It can be seen that premature birth can be detected (Tables 1, 2 and FIG. 1).
The concentration of IL-8 in the vaginal secretion is 1.5 to 12.1 ng / ml in normal pregnant women, but 41.5 to 1680 ng / ml in the imminent preterm birth group, which is significant (p-value) by the Mann-Whiteney test. <0.001) shows a high value, and it can be seen that by measuring the amount of IL-8 in vaginal secretion, vaginal secretion of an imminent prematurely delivered pregnant woman can be identified and premature birth can be detected. (Table 1, Table 2, FIG. 2).
また、血清中のＣＲＰ濃度が異常（０．８mg／dl以上）とならなかった例が、切迫早産群８例中６例存在し、血液中ＣＲＰ濃度では効果的に早産が検出されなかった。
血液中白血球数は正常値（４０００〜８０００ケ／mm3）を切迫早産群８例中３例が示し、白血球数の検査では、全ての切迫早産を検出しえなかった。
In addition, there were 6 cases in which the serum CRP concentration did not become abnormal (0.8 mg / dl or more) out of 8 cases in the premature premature birth group, and premature birth was not effectively detected in the blood CRP concentration.
The blood leukocyte count showed a normal value (4000-8000 / mm 3 ) in 3 out of 8 cases of the premature preterm birth group, and the examination of the leukocyte count did not detect any imminent premature birth.
実施例２
妊娠２５週で切迫早産と診断されトコライシス治療を行ったが、５日目に早産に至った症例を図３に示した。縦軸に膣分泌液中のＩＬ−６、ＩＬ−８濃度及び血清中ＣＲＰ濃度を示し、横軸を初診日からの日数とした。
妊婦膣分泌液中のＩＬ−６、ＩＬ−８濃度は、実施例１と同様に試料を採取し、抽出して測定した。ＩＬ−６濃度はＩＬ−６測定用ＥＬＩＳＡキット（Ｒ＆Ｄ社製）を、ＩＬ−８濃度はＩＬ−８測定用ＥＬＩＳＡキット（Ｒ＆Ｄ社製）を用いて行った。
その結果、ＩＬ−６とＩＬ−８濃度はともに上昇し続けて早産に至っており、膣分泌液中のＩＬ−６、ＩＬ−８の濃度の増加は臨床症状と一致した。しかし、従来法である血清中ＣＲＰ濃度では早産の直前にならなければ異常値とならなかった。
Example 2
FIG. 3 shows a case in which premature birth was diagnosed at 25 weeks of gestation and tocolysis treatment was performed, but premature birth resulted on the 5th day. The vertical axis shows IL-6 and IL-8 concentrations in vaginal secretions and the CRP concentration in serum, and the horizontal axis shows the number of days from the first consultation day.
The IL-6 and IL-8 concentrations in the pregnant woman's vaginal fluid were measured by extracting a sample in the same manner as in Example 1. The IL-6 concentration was measured using an IL-6 measurement ELISA kit (manufactured by R & D), and the IL-8 concentration was measured using an IL-8 measurement ELISA kit (manufactured by R & D).
As a result, both IL-6 and IL-8 concentrations continued to rise, leading to preterm birth, and the increase in IL-6 and IL-8 concentrations in vaginal secretions was consistent with clinical symptoms. However, the serum CRP concentration, which is a conventional method, did not become an abnormal value unless immediately before premature birth.
実施例３
妊娠３０週で切迫早産と診断され、トコライシス治療により満期産に至った例を図４に示した。縦軸に膣分泌液中のＩＬ−６、ＩＬ−８濃度及び血清中ＣＲＰを示し、横軸を初診日からの日数とした。妊婦膣分泌液中のＩＬ−６、ＩＬ−８濃度は、実施例１と同様に検体を採取、抽出して測定した。
症状が安定するに従い、ＩＬ−６、ＩＬ−８濃度は低下傾向を示した。治療の効果判定をモニタリングするのに膣分泌液中のＩＬ−６、ＩＬ−８濃度の測定は有効であった。
Example 3
FIG. 4 shows an example in which a premature birth was diagnosed at 30 weeks of gestation and a term was reached by tocolysis treatment. The vertical axis shows IL-6 and IL-8 concentrations in vaginal secretions and serum CRP, and the horizontal axis shows the number of days from the first consultation day. The IL-6 and IL-8 concentrations in the pregnant woman's vaginal secretion were measured by extracting and extracting a specimen in the same manner as in Example 1.
As the symptoms stabilized, the concentrations of IL-6 and IL-8 tended to decrease. Measurement of IL-6 and IL-8 levels in vaginal secretions was effective in monitoring the efficacy of treatment.
実施例４
切迫早産群の血清中のＩＬ−６及びＩＬ−８並びに膣分泌液中のＩＬ−６及びＩＬ−８の濃度変化を実施例１に準じて測定した。この結果を表３に示す。
Example 4
The changes in the concentrations of IL-6 and IL-8 in the serum of the threatened premature birth group and IL-6 and IL-8 in the vaginal secretion were measured according to Example 1. Table 3 shows the results.
血清中のＩＬ−６、ＩＬ−８量は少量であり、測定範囲下限付近であるが、膣分泌液にはＩＬ−６、ＩＬ−８は測定十分量存在する。従って局所に近い膣分泌液を試料とすることで、少量の試料で切迫早産妊婦の膣分泌液を鑑別することが可能であり、血清、血漿及び血液よりも感度よく早産を検出できる。 ＩＬThe amount of IL-6 and IL-8 in the serum is small and close to the lower limit of the measurement range, but sufficient amounts of IL-6 and IL-8 can be measured in vaginal secretions. Therefore, by using a vaginal secretion close to the topic as a sample, it is possible to distinguish the vaginal secretion of an imminent premature labor with a small amount of sample, and to detect premature labor with higher sensitivity than serum, plasma and blood.
実施例５
妊娠３０週で切迫早産と診断されトコライシス治療を行ったが、２０日目に帝王切開で早産に至った例について、実施例１と同様にしてＩＬ−６及びＩＬ−８を測定した。この結果を表４に示す。
Example 5
In a case where premature birth was diagnosed at 30 weeks of gestation and premature birth was performed by cesarean section on
初診日の検査結果から、膣分泌液中のＩＬ−６とＩＬ−８は異常と判断できる高濃度を示したが、血清中ＣＲＰ濃度と血液中白血球数は正常範囲であった。その後もＩＬ−６とＩＬ−８は高値を維持して早産に至ったが、白血球数は初診から１０日目に異常を示し、ＣＲＰ濃度においては早産直前に異常となった。このように、膣分泌液中のＩＬ−６及びＩＬ−８濃度を測定することにより、切迫早産妊婦の膣分泌液を鑑別することができ、血清中ＣＲＰ濃度や血液中の白血球数を測定するよりも早期に早産を検出できる。 検 査 From the results of the examination on the first consultation day, IL-6 and IL-8 in vaginal secretion showed high concentrations that could be judged abnormal, but serum CRP concentration and blood leukocyte count were within normal ranges. Thereafter, IL-6 and IL-8 were maintained at high levels, leading to premature birth. However, the leukocyte count showed an abnormality on the 10th day from the first consultation, and the CRP concentration became abnormal immediately before premature birth. Thus, by measuring the IL-6 and IL-8 concentrations in the vaginal secretion, the vaginal secretion of an imminent preterm delivery woman can be distinguished, and the CRP concentration in the serum and the white blood cell count in the blood are measured. Premature birth can be detected earlier than before.
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| JP7050688B2 (en) | 2016-02-05 | 2022-04-08 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Tools for predicting the risk of preterm birth |
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