| 高琪,汤威威,王宇亮,等.基于膜分离技术的夏枯草多糖调控 PI3K/Akt/NF-κB信号通路影响乳腺增生大鼠激素水平、减轻乳腺组织损伤[J].安徽医药,2026,30(9):1748-1754. |
| 基于膜分离技术的夏枯草多糖调控 PI3K/Akt/NF-κB信号通路影响乳腺增生大鼠激素水平、减轻乳腺组织损伤 |
| Prunella vulgaris polysaccharide based on membrane separation technology affects hormone levels and reduces breast tissue damage in rats with mammary gland hyperplasia by regulating PI3K/Akt/NF-κB signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2026.09.010 |
| 中文关键词: 夏枯草 多糖 乳腺增生 膜分离技术 雌二醇 PI3K/Akt/NF-κB信号通路 作用机制 |
| 英文关键词: Prunella vulgaris Polysaccharide Mammary gland hyperplasia Membrane separation technology Estradiol PI3K/Akt/NF-κB signaling pathways Mechanism of action |
| 基金项目:黑龙江省省属高等学校基本科研业务费科研项目( 2022-KYYWF-0616) |
| 作者 | 单位 | E-mail | | 高琪 | 佳木斯大学药学院,黑龙江佳木斯,154007 | | | 汤威威 | 佳木斯大学药学院,黑龙江佳木斯,154007 | | | 王宇亮 | 佳木斯大学药学院,黑龙江佳木斯,154007 | | | 沈宇 | 佳木斯大学药学院,黑龙江佳木斯,154007 | | | 王朝兴 | 佳木斯大学药学院,黑龙江佳木斯,154007 | | | 王萧鸣 | 佳木斯大学附属第一医院药学部,黑龙江佳木斯 154007 | | | 陈晨 | 佳木斯大学药学院,黑龙江佳木斯,154007 | | | 平洋 | 佳木斯大学药学院,黑龙江佳木斯,154007 | 18245482328@163.com |
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| 中文摘要: |
| 目的探讨基于膜分离技术的夏枯草多糖( PVP)对乳腺增生大鼠的影响及作用机制。方法 2021年 10月至 2022年 6月，提取 PVP，纯化后进膜组件超滤分离，测定理化性质。采用随机数字表法将 56只雌性 SD大鼠分为空白组、模型组、阳性对照组、 PVP 0~3(PVP分子量分别为 <10 kDa、10~50 kDa、>50~150 kDa及>150 kDa)组，每组 8只。除空白组外，其余各组肌内注射苯甲酸雌二醇注射液和孕酮注射液诱导乳腺增生大鼠模型。造模成功后，阳性对照组给予他莫昔芬 1.8 mg/kg，空白组和模型组灌胃给予阳性对照组同体积生理盐水， PVP 0~3组分别给予 4.14、1.87、8.08、0.89 mg/kg PVP，连续 28 d。实验结束测量大鼠乳头高度和直径，检测血清中雌二醇、孕酮、催乳素、肿瘤坏死因子 α(TNF-α)和白细胞介素 -1β(IL-1β)含量；观察大鼠乳腺组织形态学变化，蛋白质印迹法检测乳腺组织中磷脂酰肌醇 3激酶( PI3K)、磷酸化( p-)PI3K、蛋白激酶 B(Akt)、 p-Akt、核因子 κB(NF-κB)蛋白表达水平。结果经膜组件超滤分离后，得 4段 PVP，记为 PVP 0~3，理化性质及红外光谱显示 PVP 0~3均为多糖类物质。体内药理结果显示，与空白组比较，模型组大鼠乳头直径与高度，血清中雌二醇、催乳素含量均升高，孕酮含量降低(均 P<0.01)；乳腺组织导管扩张明显，腺泡数增多且直径增大；炎症因子 TNF-α、IL-1β含量升高；乳腺组织中 p-PI3K/PI3K、p-Akt/Akt和 NF-κB蛋白的表达升高(均 P<0.01)。与模型组相比，阳性对照组和 PVP 0~3组大鼠乳头直径与高度显著降低，血清中雌二醇［( 38.82±1.94)ng/L、(37.72±2.09)ng/L、(40.84±2.16)ng/L、(36.74±1.90)ng/L、(42.93±1.76)ng/L比( 52.73±2.28)ng/L］、催乳素［( 132.54±5.28)μg/L、(142.48±4.66)μg/L、(150.29±6.43)μg/L、(134.77±4.62)μg/L、(146.88±7.39)μg/L比( 183.20±6.05)μg/L］含量显著降低，孕酮［( 40.44±1.79)ng/L、(41.01±1.80)ng/L、(36.96±1.20)ng/L、(42.62±1.59)ng/L、(34.09±1.99)ng/L比( 26.71±1.78)ng/L］含量显著升高(均 P<0.01)；乳腺组织导管扩张减少或略微扩张，腺泡数目显著减少，以 PVP 2改善效果最佳； TNF-α、 IL-1β含量显著降低；乳腺组织中 p-PI3K/PI3K(1.27±0.11、1.75±0.09、2.25±0.13、1.80±0.11、2.45±0.12比 3.76±0.21)、 p-Akt/Akt(1.19±0.08、1.71±0.06、1.84±0.04、1.63±0.07、1.92±0.09比 3.13±0.09)和 NF-κB(1.05±0.08、1.55±0.09、2.08±0.10、1.23±0.07、2.43± |
| 英文摘要: |
| Objective To investigate the effect and mechanism of Prunella vulgaris polysaccharide (PVP) on rats with mammary gland hyperplasia based on membrane separation technology.Methods From October 2021 to June 2022, PVP was extracted, purifiedand then separated by ultrafiltration with membrane module, and the physicochemical properties were determined. 56 female SD ratswere divided into a blank group, a model group, a positive control group, and PVP 0-3 groups (PVP molecular weights were <10 kDa, 10-50 kDa, >50-150 kDa, and >150 kDa, respectively) using a random number table method, with 8 rats in each group. Except for theblank group, the remaining groups underwent intramuscular injection of estradiol benzoate injection and progesterone injection to in.duce a rat model of breast hyperplasia. After successful modeling, the positive control group was given tamoxifen at 1.8 mg/kg, theblank group and the model group were administered the same volume of saline by gavage as the positive control group, and the PVP 0-3 groups were administered corresponding polysaccharides at dosages of 4.14 mg/kg, 1.87 mg/kg, 8.08 mg/kg, and 0.89 mg/kg, respective.ly, for 28 consecutive days. At the end of the experiment, the height and diameter of nipples were measured, and the contents of estradi.ol (E2), progesterone (P), prolactin (PRL), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum were detected. The mor.phological changes of rat mammary tissue were observed, and the expression levels of phosphatidylinositol 3.kinase (PI3K), phosphory.lated (p.) PI3K, protein kinase B (Akt), p.Akt, and nuclear factor.κB (NF.κB) in mammary tissue were detected by Western blotting.Re. sults After ultrafiltration and separation by membrane module, four segments of PVP were obtained, which were recorded as PVP 0-3. The physicochemical properties and infrared spectrum showed that PVP 0-3 were polysaccharide substances. The in vivo pharmacologi.cal results showed that compared with the blank group, the diameter and height of the nipple, the E2 and PRL contents in the serum of the model group were increased, the P content was decreased (all P<0.01), the duct of the mammary tissue was significantly expanded,the number and diameter of acini were increased, the contents of inflammatory factors TNF-α and IL-1β were increased, and the expres. sion of p-PI3K/PI3K, p-Akt/Akt and NF-κB proteins in the mammary tissue was increased (all P<0.01). Compared with the model group, the diameter and height of nipples in the positive control group and PVP 0-3 group were significantly decreased, and the con. tents of E2 [(38.82±1.94) ng/L, (37.72±2.09) ng/L, (40.84±2.16) ng/L, (36.74±1.90) ng/L, (42.93±1.76) ng/L vs. (52.73±2.28) ng/L], PRL [(132.54±5.28) μg/L, (142.48±4.66) μg/L, (150.29±6.43) μg/L, (134.77±4.62) μg/L, (146.88±7.39) μg/L vs. (183.20±6.05) μg/L] in se.rum were significantly decreased, the contents of P [(40.44±1.79) ng/L, (41.01±1.80) ng/L, (36.96±1.20) ng/L, (42.62±1.59) ng/L,(34.09±1.99) ng/L vs. (26.71±1.78) ng/L] were significantly increased (all P<0.01). The breast tissue exhibited reduced or mildly dilat.ed ducts, with a significant decrease in the number of acini; PVP 2 demonstrated the optimal therapeutic efficacy in this regard. Thecontents of TNF-α and IL-1β were significantly decreased. The expressions of p-PI3K/PI3K (1.27±0.11, 1.75±0.09, 2.25±0.13, 1.80± 0.11, 2.45±0.12 vs. 3.76±0.21), p-Akt/Akt (1.19±0.08, 1.71±0.06, 1.84±0.04, 1.63±0.07, 1.92±0.09 vs. 3.13±0.09) and NF-κB (1.05± 0.08, 1.55±0.09, 2.08±0.10, 1.23±0.07, 2.43±0.12 vs. 3.45±0.15) proteins in breast tissue were significantly decreased (all P<0.01). Conclusion PVP can regulate the level of estrogen, reduce the degree of hyperplasia of breast tissue, and reduce the secretion of in.flammatory factors TNF-α and IL-1β, which may play a role by regulating PI3K/Akt/NF-κB signaling pathway. |
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