Role of Endogenous Prostaglandins in Vascular Remodeling

内源性前列腺素在血管重塑中的作用

• 批准号: 12671448
• 负责人: TAKAHATA Osamu
• 金额: $ 1.34万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671448/
• 关键词: prostanoids; vascular remodeling; arteriosclerosis

Mice lacking the prostaglandin (PG) I_2 receptor (IP ^<-/->) and wild-type control mice have been backcrossed to C57BL/6 mice more than 6 times, and all experiments were performed using 12-15-week-old (25-30 g) male mice. Mice were anesthetized with an intraperitoneal injection of ketamine HCl and xylazine. The left common carotid artery was ligated near the carotid bifurcation. All animals were killed 28 days after ligation of the carotid artery and fixed with 10 % formalin in PBS under constant pressure. Morphometric analyzes were performed on the carotid arteries, and the following parameters were measured: luminal area, area inside the inner elastic lamina (TEL) and area inside the external elastic lamina. The medial and intimal areas were calculated from these parameters.In non-ligated vessels, there was no difference of medial and intimal area between IP ^<-/-> mice and wild-type mice. The ratio of ligated and non-ligated intimal area was 112.9 in IP ^<-/-> mice and 3.6 in wild-type mice, respectively (P <0.0001). This ratio of medial area was 2.3 in IP ^<-/-> mice and 1.2 in wild-type mice, respectively (P<0.0001). In ligated vessels, the intimal/medial area ratio was 1.25 ± 0.34 (mean ± SE) in IP^<-/-> mice and 0.06 ± 0.03 in wild-type mice (P <0.0001). In IP ^<-/-> mice, the neointimal area as a percentage of the IEL cross section area was 58.5 ±12.4 % in IP ^<-/-> mice, which was significantly (P <0.0001) higher than that in wild-type mice (4.8 ± 2.4 %).The results show that significant suppression of ligation-induced neointimal formation by endogenous PGI_2. This means that endogenously produced PGI_2, plays an important role in ligation-induced vascular remodeling.

将前列腺素（PG）I_2受体（IP ^-/->）缺失小鼠和野生型对照小鼠与C57 BL/6小鼠回交6次以上，所有实验均使用12-15周龄（25-30 g）雄性小鼠进行。通过腹膜内注射盐酸氯胺酮和甲苯噻嗪麻醉小鼠。在颈动脉分叉附近结扎左颈总动脉。在颈动脉结扎后28天处死所有动物，并在恒定压力下用PBS中的10%福尔马林固定。对颈动脉进行形态测定分析，并测量以下参数：管腔面积、内弹性膜（TEL）内面积和外弹性膜内面积。根据这些参数计算中膜和内膜面积。在未结扎的血管中，IP ^<-/->小鼠和野生型小鼠的中膜和内膜面积没有差异。结扎和未结扎内膜面积的比率在IP ^<-/->小鼠中为112.9，在野生型小鼠中为3.6（P <0.0001）。IP ^<-/->小鼠和野生型小鼠的中膜面积比分别为2.3和1.2（P<0.0001）。在结扎的血管中，IP^<-/->小鼠的内膜/中膜面积比为1.25 ± 0.34（平均值± SE），野生型小鼠为0.06 ± 0.03（P <0.0001）。在IP ^<-/->小鼠中，新生内膜面积占IEL横截面积的百分比在IP ^<-/->小鼠中为58.5 ± 12.4%，其显著（P <0.0001）高于野生型小鼠（4.8 ± 2.4%）。提示内源性PGI_2在结扎诱导的血管重构中起重要作用。

项目成果

Ma, H., Hara A., Xiao, C.-Y., Okada, Y., Takahata O., Nakaya.K., Sugimoto, Y., Ichikawa, A., Narumiya.S., Ushikubi, F.: "Increased bleeding tendency and decreased susceptibility to thromboembolism in mice lacking the prostaglandin E receptor subtype EP_3"

Ma，H.，Hara A.，肖，C.-Y.，冈田，Y.，高畠O.，Nakaya.K.，杉本，Y.，市川，A.，Narumiya.S.，Ushikubi，F.

Shuanglin Hao, Osamu Takahata, Hiroshi Iwasaki: "Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: an isobolographic analysis"Anesthesia and Analgesia. 92. 733-738 (2001)

双林浩，Osamu Takahata，Hiroshi Iwasaki：“大鼠福尔马林试验中脊髓可乐定和利多卡因之间的抗伤害相互作用：等辐射线分析”麻醉和镇痛。

O. Takahata, T. Fujino, A. Hara, F. Ushikubi and H. Iwasaki: "Role of Endogenous Prostaglandin I_2 in Vascular Remodeling"Anesthesiology. 95. A632-A632 (2001)

O. Takahata、T. Fujino、A. Hara、F. Ushikubi 和 H. Iwasaki：“内源性前列腺素 I_2 在血管重塑中的作用”麻醉学。

O.Takahata, T.Fujino, A.Hara, F.Ushikubi, H.Iwasaki: "Role of Endogenous Prostaglandin I_2 in Vascular Remodeling"Anesthesiology. 95. A632 (2001)

O.Takahata、T.Fujino、A.Hara、F.Ushikubi、H.Iwasaki：“内源性前列腺素 I_2 在血管重塑中的作用”麻醉学。

Xiao, C.-Y., Hara, A., Yuhki, K., Fujino, T., Ma, H., Okada, Y., Takahata, O., Yamada, T., Murata, T., Narumiya, S., Ushikubi, F.: "Roles of prostaglandin I_2 and thromboxane A_2 in cardiac ischemia-reperfusion injury : a study using mice lacking their re

肖，C.-Y.，原，A.，Yuhki，K.，藤野，T.，马，H.，冈田，Y.，高畑，O.，山田，T.，村田，T.，Narumiya，