400038 重庆,陆军军医大学(第三军医大学)第一附属医院消化内科
Received:13 October 2022,
Revised:2022-12-06,
Published:30 January 2023
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Yalan SONG, Tianyu WU, Cong CHEN, et al. Expression and role of PD-L1 in colonic mucosa of ulcerative colitis patients and DSS-induced colitis mouse model[J]. Journal of Army Medical University, 2023, 45(2): 155-164.
Yalan SONG, Tianyu WU, Cong CHEN, et al. Expression and role of PD-L1 in colonic mucosa of ulcerative colitis patients and DSS-induced colitis mouse model[J]. Journal of Army Medical University, 2023, 45(2): 155-164. DOI: 10.16016/j.2097-0927.202210100.
2
探讨细胞程序性死亡配体-1(programmed cell death-ligand 1
PD-L1)在溃疡性结肠炎(ulcerative colitis
UC)发病机制中的作用。
方法
2
收集2022年1-9月于陆军军医大学第一附属医院消化内科肠镜室就诊的18~64岁的UC患者结肠组织标本29例
同期收集非UC患者结肠组织标本22例
采用免疫组化和RT-qPCR检测
PD
-
L
1和炎症因子
IL
-1
β
、
IL
-6、
IL
-17
a
、
IL
-22、
TGF
-
β
1的表达。选取8~10周龄C57BL/6雄性小鼠24只(23~26 g)
分为空白对照组(
n
=4)、PD-L1-Fc组(
n
=4)、葡聚糖硫酸钠(dextran sulfate sodium salt
DSS)组(
n
=8)、DSS+PD-L1-Fc组(
n
=8)
DSS组及DSS+PD-L1-Fc组连续7天予以2.5% DSS溶液自由饮水
第8天更换为正常饮水
其余组
正常饮水
第3天予以PD-L1-Fc组及DSS+PD-L1-Fc组小鼠腹腔注射PD-L1-Fc蛋白(1 mg/mL)40μg/只
造模后8~10天检测各组小鼠结肠黏膜中PD-L1的表达情况
并观察各组小鼠的体质量、粪便性状、活体结肠黏膜形态变化、组织病理学改变及炎症因子改变情况。
结果
2
与对照组相比
UC患者结肠黏膜中PD-L1表达显著升高(43.03±4.044
P
<
0.001)
促炎因子
IL
-1
β
、
IL
-6及抗炎因子
IL
-22、
TGF
-
β
1的表达均升高(
P
<
0.05);在DSS小鼠模型中同样存在这一现象。腹腔注射PD-L1-Fc蛋白后
DSS小鼠的体质量、粪便评分、结肠黏膜大体形态及显微镜下炎症程度明显改善(
P
<
0.05)
IL
-6、
IL
-17
a
下调(
P
<
0.05)
IL
-22、
Foxp
3上调(
P
<
0.05)。
结论
2
PD
-
L
1在UC患者及小鼠DSS结肠炎模型中升高
可能是机体的一种适应性保护作用。
Objective
2
To explore the role of programmed cell death-ligand 1(PD-L1) in pathogenesis of ulcerative colitis (UC).
Methods
2
A total of 29 colon tissue samples from UC patients aged 18~64 years who underwent the colonoscopy in our department from January 2022 to September 2022 were collected
and another 22 colon tissue samples from non-UC patients were also collected during the same period.The expression of
PD
-
L
1 and inflammatory factors
IL
-1
β
IL
-6
IL
-17
a
IL
-22 and
TGF
-
β
1 were detected by immunohistochemistry and RT-qPCR.Twenty-four male C57BL/6 mice (8~10 weeks old
23~26 g) were randomly divided into blank control group (
n
=4)
PD-L1-Fc group (
n
=4)
dextran sulfate sodium salt (DSS) group (
n
=8)
and DSS+PD-L1-Fc group (
n
=8).The mice from the DSS group and DSS+PD-L1-Fc group were given 2.5% DSS solution for 7 consecutive days
and were chang
ed to normal drinking water on the 8th day.The animals of the other groups were given normal drinking water.On the 3rd day
the mice in the PD-L1-Fc group and DSS+PD-L1-Fc group were injected intraperitoneally with PD-L1-Fc protein (1 mg/mL
40 μg/animal).In 8~10 d after modeling
the expression of
PD
-
L
1 in colonic mucosa was detected
and the body weight
fecal traits
morphological changes
histopathological changes and inflammatory factors were observed in different groups.
Results
2
The expression of
PD
-
L
1 was significantly increased in the colonic mucosa of UC patients (43.03±4.044
P
<
0.001) than of normal colon tissue samples
and the expression of pro-inflammatory factors
IL
-1
β
and
IL
-6 and anti-inflammatory factors
IL
-22 and
TGF
-
β
1 were increased (
P
<
0.05)
which also existed in DSS mouse models.Intraperitoneal injection of PD-L1-Fc protein improved body weight
fecal score
gross morphology of colonic mucosa and microscopic inflammation (
P
<
0.05)
down-regulated
IL
-6 and
IL
-17
a
(
P
<
0.05) and up-regulated
IL
-22 and
Foxp
3(
P
<
0.05) in the DSS+PD-L1-Fc mice when compared with the DSS group.
Conclusion
2
The upregulation of
PD
-
L
1 in UC patients and DSS-induced colitis mouse models may play an adaptive protective role.
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