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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年02期

页码:

160-164

栏目:

基础医学

出版日期:

2022-03-20

文章信息/Info

Title:

Potential role of chronic inflammation in persistent ovarian injury exposed to X-ray targeted irradiation in rhesus monkeys

文章编号:

1006-8147(2022)02-0160-05

作者:

周莹¹; 杜湧瑞¹; Mary B. Zelinski²; 王建梅¹

（1.天津医科大学第二医院计划生育科，天津300211；2.美国俄勒冈健康与科学大学生殖科学部，俄勒冈 97006）

Author(s):

ZHOU Ying¹; DU Yong-rui¹; Mary B. Zelinski²; WANG Jian-mei¹

（1.Department of Family Planning，The Second Hospital，Tianjin Medical University，Tianjin 300211，China； 2.Division of Reproductive Sciences，Oregon National Primate Research Center，Oregon Health & Science University，Beaverton，Oregon 97006，USA ）

关键词:

放射治疗; 慢性炎症; 恒河猴; 卵巢损伤;  FTY-720

Keywords:

radiotherapy; chronic inflammation; rhesus monkeys; ovarian damage; FTY-720

分类号:

R711.75

DOI:

-

文献标志码:

A

摘要:

目的：探讨在X射线诱发恒河猴卵巢损伤中慢性炎症是否发挥重要作用。方法：14只月经周期规律的成年雌性恒河猴（8～14岁），随机分为3组（3只/组）：假照射（Sham）组（n=8）、卵巢照射（OXI） 组（n=3）、X射线照射+FTY-720（免疫抑制剂）（FTY-720）组（n=3）。Sham组给与溶剂PET+假手术（保留卵巢血管蒂，将卵巢移出腹腔），OXI组动物卵巢移出腹腔后给与15 Gy X射线照射，FTY-720组卵巢内行0.2 mmol/L FTY-720灌注1周后给与15 Gy X射线照射。各组手术操作相同，结束后将卵巢复位，均于早卵泡期行卵巢组织取材[照射结束后第（316±7）天]。免疫组织化学染色法检测卵巢组织单核细胞趋化蛋白-1（MCP-1）、CD11b和CD68的表达并计数CD11b、CD68阳性细胞，ELISA法检测照射结束后第３个月和第９个月血清MCP-1、白细胞介素（IL）-6水平。结果：OXI组卵巢组织MCP-1阳性染色强于Sham组和FTY-720组，而FTY-720组MCP-1表达与Sham组表达情况相似。与Sham组相比，OXI组CD11b阳性细胞数量明显增多（P<0.05）；而FTY-720组CD11b阳性细胞数量明显少于OXI组（P<0.05），且其与Sham组相比较，差异无统计学意义（P>0.05）。3组间CD68阳性细胞数量差异无统计学意义（P>0.05），但观察到OXI组卵巢组织CD68阳性细胞数量呈增高趋势，而FTY-720组变化不明显，接近Sham组水平。照射后第３个月，3组间血清MCP-1浓度差异不显著（P >0.05）；第９个月时，OXI组MCP-1浓度明显高于Sham组（P=0.031 4），而FTY-720组明显低于OXI组（P=0.017 2）。血清IL-6仅在OXI组中检测到，照射后第３个月时为（4±1） pg/mL，９个月时为（9±6） pg/mL（P >0.05）。结论：X射线照射可诱发卵巢慢性炎症，而FTY-720能够抑制该炎症，降低恒河猴卵巢组织内MCP-1的表达、CD11b+和CD68+巨噬细胞的浸润，减少血清MCP-1、IL-6含量。

Abstract:

Objective： To explore whether chronic inflammation plays a vital role in X-ray-induced ovarian injury in rhesus monkeys. Methods: Fourteen healthy adult female rhesus monkeys（8-14 years old） with regular menstrual cycle were randomly assigned to 3 groups: sham irradiation（Sham） group（n=8），ovarian X-rays irradiation（OXI） group（n=3） and ovarian X-rays irradiation+FTY-720 （FTY-720） group（n=3）. In Sham group，the ovary，with preserving the vascular pedicel，was moved out of body（Sham operation） after the solvent PET intraovarian perfusion. In the OXI group，the ovary with preserving the vascular pedicel was moved out of body and was given 15 Gy X-ray irradiation. In the FTY-720 group，the ovary with preserving the vascular pedicel was moved out of body and was given 15 Gy X-ray irradiation after the 0.2 mmol/L FTY-720 intraovarian perfusion for one week. At the end of the operation，the ovaries were put back in place. At the early follicular phase[（316±7） d after irradiation]，the animals were euthanized and their ovaries were collected. Immunohistochemistry was performed to evaluate monocyte chemoattractant protein-1（MCP-1），CD11b，CD68 expression and CD11b and CD68 positive cells were counted. ELISA was used to detect MCP-1 and IL-6 in serum at the 3rd and 9th month after irradiation. Results: The positive staining of MCP-1 in ovarian tissue of OXI group was higher than that of Sham group and FTY-720 group，while the expression of MCP-1 in FTY-720 group was similar to that of Sham group. Compared with the Sham group，the number of CD11b positive cells in the OXI group was significantly increased（P<0.05）； while in FTY-720 group was significantly less than that in OXI group（P<0.05），but there was no statistical significance between FTY-720 group and Sham group（P>0.05）. Although there was no significant difference in the number of CD68-positive cells among the three groups（P>0.05），it was observed that the number of CD68-positive cells in ovarian tissue of OXI group showed an increasing trend，while that of FTY-720 group had no significant change，which was close to the level of Sham group. There was no significant difference in serum MCP-1 level among the three groups（P>0.05） at the 3rd month after irradiation，but at the 9th month，the MCP-1 concentration in the OXI group was significantly higher than that of the Sham group （P=0.031 4），while the serum MCP-1 concentration of the FTY-720 group was significantly lower than that of the OXI group（P=0.017 2）. Serum IL-6 was detected only in the serum of rhesus monkeys in the OXI group，which was （4±1） pg/mL at the 3rd month and（9±6） pg/mL at the 9th month after irradiation. Conclusion： X-ray irradiation can induce chronic inflammation of ovary，but FTY-720 can inhibit this inflammatory reaction，reduce the expression of MCP-1，the infiltration of CD11b+ and CD68+ macrophages in ovarian tissue of rhesus monkey，and reduce the content of serum MCP-1 and IL-6.

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相似文献/References:

备注/Memo

备注/Memo:

作者简介 周莹（1995-），女，硕士在读，研究方向：卵巢早衰，辅助生殖，生育力保存/保护；通信作者：王建梅，E-mail：wangjianmei@tmu.edu.cn。

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更新日期/Last Update: 2022-03-20