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第45卷第4期 林俊杰，王 舒，赵小静，等. 双调蛋白通过上调LPA⁃LPAR3调控肠成纤维细胞活化促进克
2025年4月 罗恩病肠纤维化［J］. 南京医科大学学报（自然科学版），2025，45（4）：498-508 ·505 ·

A B Control⁃siRNA Control⁃siRNA+LPA LPAR3⁃siRNA+LPA LPAR3⁃siRNA C
1.5 （μm 2 ） 800 000 *** **

LPAR3 relative expression 1.0 0 h 72 μm 72 μm 72 μm 72 μm Migration area 600 000
400 000
0.5
200 000
0
Control⁃siRNA LPAR3⁃siRNA 48 h Control⁃siRNA 0 - + + + - - -
LPA
+
LPAR3⁃siRNA - - + +
72 μm 72 μm 72 μm 72 μm
E 2.0 ** **

Relative 1.0
D α⁃SMA expression 1.5
α⁃SMA 42 kDa 0.5
GAPDH 36 kDa 0
LPA - + + - LPA - + + -
Control⁃siRNA + + - - Control⁃siRNA + + - -
LPAR3⁃siRNA - - + + LPAR3⁃siRNA - - + +
F 4 G H
4 ** * 6 ** *
*
**
3
Col1a1 relative expression 2 1 Col6a1 relative expression 3 2 Col6a3 relative expression 4 2

0 1 0 0
LPA - + + - LPA - + + - LPA - + + -
Control⁃siRNA + + - - Control⁃siRNA + + - - Control⁃siRNA + + - -
LPAR3⁃siRNA - - + + LPAR3⁃siRNA - - + + LPAR3⁃siRNA - - + +
I J 40 ** **
Control⁃siRNA Control⁃siRNA+LPA LPAR3⁃siRNA+LPA LPAR3⁃siRNA 30
Percentage of positive cells 20

Ki67/DAPI Ki67 10

0
LPA - + + -
20 μm 20 μm 20 μm 20 μm Control⁃siRNA + + - -
LPAR3⁃siRNA - - + +

A：The expression of LPAR3 of fibroblasts after treating with LPAR3⁃siRNA or control⁃siRNA was measured by qRT⁃PCR（n=3）. B，C：The
migration ability of fibroblasts after treating with LPA while with LPAR3⁃siRNA or control⁃siRNA was assessed by the wound healing assay（n=9）. D，E：The
expression of α⁃SMA in fibroblasts after treating with LPA while with LPAR3⁃siRNA or control⁃siRNA was detected by Western blot（n=3）. F-H：The
expression of Col1a1（F），Col6a1（G），and Col6a3（H）of fibroblasts after treating with LPA while with LPAR3⁃siRNA or control⁃siRNA was measured
by qRT⁃PCR（n=3）. I，J：Fibroblasts were stained with Ki67 immunofluorescence and percentage of Ki67 positive cells were calculated（scale bar=
**
*
100 μm，n=3）. P < 0.05，P < 0.01，and *** P < 0.001.
图5 LPA通过LPAR3促进人肠成纤维细胞的运动、活化和增殖
Figure 5 LPA promoted the motility，activation，and proliferation of human intestinal fibroblasts via LPAR3

AREG⁃LPA⁃LPAR3可能是治疗CD相关肠纤维化的 道狭窄和梗阻，是患者手术的主要原因，目前尚缺
潜在靶点。 乏有效的抗肠道纤维化的治疗手段 ，深入探究肠纤
［5］
维化的发病机制将为寻求新的治疗靶点提供思路。
3 讨 论
纤维化是损伤后组织修复和再生过程中的一部分。
肠纤维化是 CD 常见的并发症之一，可导致肠 过度沉积的ECM是纤维化的典型特征，成纤维细胞