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武汉市中医医院肾病科,武汉 430014
Published:30 March 2024,
Received:07 October 2023,
Revised:01 March 2024,
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冯雪,彭斌,冯立等.黄芪多糖对腹膜透析大鼠腹膜纤维化和血管生成的影响及机制 Δ[J].中国药房,2024,35(06):712-717.
FENG Xue,PENG Bin,FENG Li,et al.Effect and mechanism of Astragalus polysaccharide on peritoneal fibrosis and angiogenesis in peritoneal dialysis rats[J].ZHONGGUO YAOFANG,2024,35(06):712-717.
冯雪,彭斌,冯立等.黄芪多糖对腹膜透析大鼠腹膜纤维化和血管生成的影响及机制 Δ[J].中国药房,2024,35(06):712-717. DOI: 10.6039/j.issn.1001-0408.2024.06.13.
FENG Xue,PENG Bin,FENG Li,et al.Effect and mechanism of Astragalus polysaccharide on peritoneal fibrosis and angiogenesis in peritoneal dialysis rats[J].ZHONGGUO YAOFANG,2024,35(06):712-717. DOI: 10.6039/j.issn.1001-0408.2024.06.13.
目的
2
探讨黄芪多糖(APS)对腹膜透析(PD)大鼠腹膜纤维化和血管生成的影响及机制。
方法
2
将大鼠分为正常对照组(Control组)、模型组(PD组)、70 mg/kg APS组(APS-L组)、140 mg/kg APS组(APS-H组)、140 mg/kg APS+40 mg/kg缺氧诱导因子1α(HIF-1α)激动剂DMOG组(APS-H+DMOG组),每组12只。后4组大鼠构建PD大鼠模型。各给药组大鼠灌胃相应剂量的APS及腹腔注射相应剂量的DMOG,Control组和PD组大鼠灌胃等体积生理盐水,每天给药1次,连续4周。末次给药后,检测大鼠腹膜超滤量(UF)、葡萄糖转运量(MTG)和血清中肌酐(Scr)、尿素氮(BUN)水平;观察腹膜组织病理学变化和纤维化情况(腹膜厚度和胶原纤维沉积占比);检测腹膜组织微血管密度和
α
-平滑肌肌动蛋白(
α
-SMA)、层粘连蛋白(LN)、HIF-1α、血管内皮生长因子(VEGF)蛋白表达水平。
结果
2
与Control组比较,PD组大鼠间皮细胞结构疏松,腹膜间皮细胞脱落,炎症细胞浸润,腹膜厚度和胶原纤维沉积占比均显著增加(
P
<0.05);MTG,血清中Scr、BUN水平,腹膜组织微血管密度和
α
-SMA、LN、HIF-1α、VEGF蛋白表达水平均显著升高,而UF显著降低(
P
<0.05);与PD组比较,APS-L组、APS-H组大鼠上述指标均显著改善(
P
<0.05),其中APS-H组改善效果优于APS-L组(
P
<0.05);与APS-H组比较,APS-H+DMOG组大鼠上述指标变化均逆转(
P
<0.05)。
结论
2
APS可以通过抑制HIF-1α/VEGF信号通路来抑制PD大鼠腹膜纤维化及血管新生。
OBJECTIVE
2
To investigate the effect and mechanism of
Astragalus
polysaccharide (APS) on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis (PD).
METHODS
2
Rats were randomly divided into normal control group (Control group), model group (PD group), 70 mg/kg APS group (APS-L group), 140 mg/kg APS group (APS-H group), and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α (HIF-1α) agonist DMOG group (APS-H+DMOG group), with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically, once a day, for 4 consecutive weeks. After the last medication, the peritoneal ultrafiltration (UF), mass transfer of glucose (MTG), the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected in rats; peritoneal histomorphology and peritoneal fibrosis (peritoneal thickness and proportion of collagen fiber deposition) were observed; the microvascular density and the expression levels of
α
-smooth muscle actin (
α
-SMA), laminin (LN), HIF-1α and vascular endothelial growth factor (VEGF) proteins were detected in peritoneal tissue of rats.
RESULTS
2
Compared with Control group, the mesothelium of rats in the PD group was loosely arranged and shed, inflammatory cells infiltrated, the peritoneal thickness and proportion of collagen fiber deposition were increased significantly (
P
<0.05). The levels of MTG, Scr and BUN in serum, microvascular density and the expressions of
α
-SMA, LN, HIF-1α and VEGF proteins were significantly increased, while the level of UF was significantly decreased (
P
<0.05); compared with PD group, the levels of above indexes were significantly reversed in APS-L and APS-H groups (
P
<0.05), and the improvement of APS-H group was better than APS-L group (
P
<0.05). Compared with APS-H group, the levels of above indexes in APS-H+DMOG group were all reversed (
P
<0.05).
CONCLUSIONS
2
APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.
黄芪多糖缺氧诱导因子-1α/血管内皮生长因子信号通路腹膜透析腹膜纤维化血管生成
HIF-1α/VEGF signaling pathwayperitoneal dialysisperitoneal fibrosisangiogenesis
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