【摘要】：目的探討多烯磷脂酰膽堿對奧沙利鉑聯(lián)合氟尿嘧啶所致肝損傷的保護(hù)作用。方法 30只BALB/c裸鼠皮下種植結(jié)腸癌HCT116細(xì)胞制備荷瘤裸鼠模型,隨機(jī)分為3組:肝損傷組,實驗首日腹腔注射奧沙利鉑(6 mg·kg~(-1)·d~(-1))0.2 mL,同時連續(xù)7 d腹腔注射氟尿嘧啶(20 mg·kg~(-1)·d~(-1));多烯磷脂酰膽堿組,在給予等量氟尿嘧啶和奧沙利鉑前30 min,腹腔注射多烯磷脂酰膽堿(85 mg·kg~(-1)·d~(-1))0.2 mL,共7 d;荷瘤空白組,注射生理鹽水作為對照。取各組裸鼠肝臟,石蠟切片,HE染色,光學(xué)顯微鏡下觀察肝臟組織的變化;制作超薄切片,電子顯微鏡下觀察肝細(xì)胞超微結(jié)構(gòu)的變化;制作10%肝組織勻漿,黃嘌呤氧化酶法檢測肝組織超氧化物歧化酶(SOD)活性,比色法檢測過氧化氫酶(CAT)活性。結(jié)果肝損傷組裸鼠肝臟的胞質(zhì)局部溶解,線粒體膜破損,細(xì)胞核膜水腫模糊,肝竇擴(kuò)張,多烯磷脂酰膽堿部分逆轉(zhuǎn)了這些損傷。與荷瘤空白組相比,肝損傷組SOD和CAT的表達(dá)明顯降低(P0.05);與肝損傷組相比,多烯磷脂酰膽堿組SOD和CAT的表達(dá)升高(P0.05)。說明多烯磷脂酰膽堿能減輕化療藥物對肝臟的毒性作用,抑制氧化應(yīng)激反應(yīng)。結(jié)論多烯磷脂酰膽堿對氟尿嘧啶聯(lián)合奧沙利鉑引起的肝損傷具有預(yù)防、保護(hù)作用,該作用可能與其膜修復(fù)和抗氧化應(yīng)激反應(yīng)的作用有關(guān)。
[Abstract]:Objective to investigate the protective effect of polyene phosphatidylcholine on liver injury induced by oxaliplatin and fluorouracil. Methods Thirty nude BALB/c nude mice with colon cancer HCT116 cells implanted subcutaneously were randomly divided into 3 groups: liver injury group. On the first day of the experiment, oxaliplatin (6 mg kg~ (-1) d ~ (-1) 0.2 mL,) was injected intraperitoneally. Fluorouracil (20 mg kg~ (-1) d ~ (-1);) was injected intraperitoneally for 7 days at the same time. In the polyenylphosphatidylcholine group, intraperitoneal injection of polyenylphosphatidylcholine (85 mg kg~ (-1) d-1) 0.2 mL, for 7 days was performed 30 min, before the same dose of fluorouracil and oxaliplatin. The control group was injected with normal saline. The liver, paraffin sections, HE staining and optical microscope were used to observe the changes of liver tissue, ultrathin sections and ultrastructure of hepatocytes were observed under electron microscope. The activity of superoxide dismutase (SOD) was detected by xanthine oxidase method and the activity of catalase (CAT) was detected by colorimetry. Results in the liver injury group, the cytoplasm of the liver was partially dissolved, the mitochondria membrane was damaged, the nuclear membrane edema was blurred, the hepatic sinusoid dilated, and the damage was partially reversed by polyenylphosphatidylcholine. Compared with the control group, the expression of SOD and CAT in liver injury group was significantly lower (P0.05); compared with liver injury group, the expression of SOD and CAT in polyene phosphatidylcholine group was higher than that in liver injury group (P0.05). The results showed that Polyene phosphatidylcholine could reduce the toxic effect of chemotherapeutic drugs on liver and inhibit oxidative stress reaction. Conclusion Polyene phosphatidylcholine can prevent and protect liver injury induced by fluorouracil and oxaliplatin, which may be related to membrane repair and antioxidant stress response.
【作者單位】： 中國醫(yī)科大學(xué)附屬盛京醫(yī)院腫瘤科;
【基金】：沈陽市科學(xué)技術(shù)計劃(F13-316-1-69)
【分類號】：R735.34

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