南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (2): 293-300.doi: 10.12122/j.issn.1673-4254.2026.02.07
• • 上一篇
邱佳惠1(
), 陈萌2(
), 满如3, 陈鑫1, 邱东瑞1, 常启同1, 马洪玉1
收稿日期:2025-07-16
出版日期:2026-02-20
发布日期:2026-03-10
通讯作者:
陈萌
E-mail:3010057273@qq.com;187362783@qq.com
作者简介:邱佳惠,在读硕士研究生,E-mail: 3010057273@qq.com
基金资助:
Jiahui QIU1(
), Meng CHEN2(
), Ru MAN3, Xin CHEN1, Dongrui QIU1, Qitong CHANG1, Hongyu MA1
Received:2025-07-16
Online:2026-02-20
Published:2026-03-10
Contact:
Meng CHEN
E-mail:3010057273@qq.com;187362783@qq.com
Supported by:摘要:
目的 基于磷脂酰肌醇-3-激酶蛋白激酶B(PI3K/Akt)信号通路,通过对慢传输型便秘(STC)大鼠结肠Cajal间质细胞(ICCs)胞葬过程的变化进行评价,探索化瘀通便汤对慢传输型便秘的作用机制。 方法 取SD大鼠采用盐酸洛哌丁胺混悬液灌胃法制备STC模型,随机分为模型组、化瘀通便汤中药低剂量组、化瘀通便汤中药中剂量组、化瘀通便汤中药高剂量组、阳性药物(莫沙必利)组,每组12只,另取12只SD大鼠灌胃等剂量生理盐水设为空白组。测量各组大鼠首次黑便时间、粪便含水率、肠道推进率;通过透射电镜观察分析Cajal间质细胞超微结构,计算线粒体空泡率;免疫荧光实验检测各组大鼠巨噬细胞吞噬率;HE染色检测各组大鼠结肠病理形态;免疫组织化学(IHC)染色检测各组大鼠结肠组织酪氨酸蛋白激酶受体(c-Kit)表达水平;Western blotting法检测大鼠结肠c-Kit、整联蛋白相关蛋白(CD47)、PI3K、Akt蛋白含量,分析各项指标与胞葬作用的相关性。 结果 与空白组比较,模型组大鼠出现典型的便秘症状,Cajal间质细胞超微结构明显损坏,大鼠结肠黏膜出现明显病理损伤,首次黑便时间、线粒体空泡率、CD47、p-PI3K/PI3K、p-Akt/Akt蛋白表达水平明显升高(P<0.01),粪便含水率、肠道推进率、c-Kit蛋白表达水平明显降低(P<0.01),吞噬率两组无明显差异。与模型组比较,化瘀通便汤中药各剂量组大鼠Cajal间质细胞超微结构形态基本正常,大鼠结肠黏膜病理损伤明显减轻,粪便含水率、肠道推进率、吞噬率、c-Kit蛋白表达明显升高(P<0.05),首次黑便时间、线粒体空泡率、CD47、p-PI3K/PI3K、p-Akt/Akt蛋白含量均降低(P<0.05),其中,化瘀通便汤中药高剂量组结果最为显著(P<0.01)。 结论 化瘀通便汤可能通过抑制PI3K、Akt的磷酸化,下调CD47蛋白表达,提高巨噬细胞吞噬率,从而促进Cajal间质细胞的胞葬过程,发挥对慢传输型便秘的治疗作用。
邱佳惠, 陈萌, 满如, 陈鑫, 邱东瑞, 常启同, 马洪玉. 化瘀通便汤通过抑制PI3K/Akt信号通路促进慢传输型便秘大鼠肠道Cajal间质细胞的胞葬作用[J]. 南方医科大学学报, 2026, 46(2): 293-300.
Jiahui QIU, Meng CHEN, Ru MAN, Xin CHEN, Dongrui QIU, Qitong CHANG, Hongyu MA. Huayu Tongbian Decoction promotes efferocytosis of interstitial Cajal cells in rats with slow transit constipation by inhibiting the PI3K/Akt signaling pathway[J]. Journal of Southern Medical University, 2026, 46(2): 293-300.
| Group | Before modeling | After modeling | After treatment |
|---|---|---|---|
| Control | 212.15±1.20 | 248.86±3.48 | 309.82±5.85 |
| Model | 213.67±3.67 | 231.83±1.56** | 267.00±2.81** |
| LH | 210.77±3.81 | 230.05±2.17** | 272.54±6.19** |
| MH | 208.41±2.94 | 230.11±2.53** | 284.46±6.37**# |
| HH | 210.87±2.50 | 230.66±2.13** | 297.07±5.14## |
| Positive drug | 208.04±2.53 | 227.84±1.61** | 291.82±8.19*## |
表1 各组大鼠体质量变化
Tab.1 Changes in body weight of the rats in each group (g, Mean±SD, n=10)
| Group | Before modeling | After modeling | After treatment |
|---|---|---|---|
| Control | 212.15±1.20 | 248.86±3.48 | 309.82±5.85 |
| Model | 213.67±3.67 | 231.83±1.56** | 267.00±2.81** |
| LH | 210.77±3.81 | 230.05±2.17** | 272.54±6.19** |
| MH | 208.41±2.94 | 230.11±2.53** | 284.46±6.37**# |
| HH | 210.87±2.50 | 230.66±2.13** | 297.07±5.14## |
| Positive drug | 208.04±2.53 | 227.84±1.61** | 291.82±8.19*## |
| Group | Fecal water content (%) | First black stool time (min) | Intestinal propulsion rate (%) |
|---|---|---|---|
| Control | 55.11±1.17 | 186.20±3.59 | 80.37±2.61 |
| Model | 26.71±0.63** | 302.20±10.13** | 48.20±1.15** |
| LH | 29.40±1.17** | 288.70±8.63** | 51.83±1.93** |
| MH | 42.73±1.20**## | 260.70±6.68**## | 66.50±2.01**## |
| HH | 52.25±1.31## | 198.30±11.43## | 76.07±1.74## |
| Positive drug | 44.17±1.00**## | 246.20±6.26**## | 66.90±1.57**## |
表2 各组大鼠粪便含水率、首次黑便时间及肠道推进率
Tab.2 Fecal water content, first black stool time and intestinal propulsion rate of the rats in each group (Mean±SD, n=10)
| Group | Fecal water content (%) | First black stool time (min) | Intestinal propulsion rate (%) |
|---|---|---|---|
| Control | 55.11±1.17 | 186.20±3.59 | 80.37±2.61 |
| Model | 26.71±0.63** | 302.20±10.13** | 48.20±1.15** |
| LH | 29.40±1.17** | 288.70±8.63** | 51.83±1.93** |
| MH | 42.73±1.20**## | 260.70±6.68**## | 66.50±2.01**## |
| HH | 52.25±1.31## | 198.30±11.43## | 76.07±1.74## |
| Positive drug | 44.17±1.00**## | 246.20±6.26**## | 66.90±1.57**## |
图1 化瘀通便汤对STC大鼠结肠ICCs超微结构的影响
Fig.1 Effect of Huayu Tongbian Decoction on ultrastructure of interstitial Cajal cells (ICCs) in the colon tissues of rat models of slow transit constipation (STC) (Original magnification: ×20 000). The black arrow indicates the nucleus, the red thin arrow indicates the mitochondria, the red thick arrow the lysosome, and the blue thin arrow the endoplasmic reticulum.
| Group | Mitochondrial vacuolation rate (%) |
|---|---|
| Control | 15.15±0.93 |
| Model | 69.28±4.81** |
| LH | 64.88±1.18** |
| MH | 59.26±3.76**# |
| HH | 34.01±2.99**## |
| Positive drug | 45.98±1.21**## |
表3 各组大鼠线粒体空泡率
Tab.3 Mitochondrial vacuolation rate of the rats in each group (Mean±SD, n=5)
| Group | Mitochondrial vacuolation rate (%) |
|---|---|
| Control | 15.15±0.93 |
| Model | 69.28±4.81** |
| LH | 64.88±1.18** |
| MH | 59.26±3.76**# |
| HH | 34.01±2.99**## |
| Positive drug | 45.98±1.21**## |
| Group | Phagocytosis rate (%) |
|---|---|
| Control | 1.84±0.89 |
| Model | 6.94±0.40 |
| LH | 11.06±1.00** |
| MH | 32.69±1.94**## |
| HH | 51.21±3.14**## |
| Positive drug | 24.60±1.75**## |
表4 各组大鼠胞葬水平
Tab.4 Efferocytosis level of the rats in each group (Mean±SD, n=5)
| Group | Phagocytosis rate (%) |
|---|---|
| Control | 1.84±0.89 |
| Model | 6.94±0.40 |
| LH | 11.06±1.00** |
| MH | 32.69±1.94**## |
| HH | 51.21±3.14**## |
| Positive drug | 24.60±1.75**## |
图4 化瘀通便汤对STC大鼠结肠组织c-Kit蛋白表达的影响
Fig.4 Effect of Huayu Tongbian Decoction on expressions of c-Kit protein in the colon tissue of STC rats (HE staining, ×200).
| Group | c-Kit(AOD) |
|---|---|
| Control | 0.34±0.011 |
| Model | 0.20±0.011** |
| LH | 0.22±0.008** |
| MH | 0.24±0.005**## |
| HH | 0.32±0.003## |
| Positive drug | 0.28±0.008**## |
表5 各组大鼠结肠组织c-Kit蛋白水平比较
Tab.5 Comparison of c-Kit protein levels in the colon tissue of the rats in each group (Mean±SD, n=3)
| Group | c-Kit(AOD) |
|---|---|
| Control | 0.34±0.011 |
| Model | 0.20±0.011** |
| LH | 0.22±0.008** |
| MH | 0.24±0.005**## |
| HH | 0.32±0.003## |
| Positive drug | 0.28±0.008**## |
图5 化瘀通便汤对STC大鼠c-Kit、CD47、p-PI3K、PI3K、p-Akt、Akt蛋白表达的影响
Fig.5 Effect of Huayu Tongbian Decoction on c-Kit, CD47, p-PI3K, PI3K, p-Akt and Akt protein expressions detected by Western blotting in STC rats.
| Group | c-Kit/β-actin | CD47/β-actin | p-PI3K/PI3K | p-Akt/Akt |
|---|---|---|---|---|
| Control | 3.37±0.05 | 0.59±0.05 | 0.53±0.10 | 0.47±0.02 |
| Model | 1.24±0.14** | 1.26±0.07** | 1.24±0.02** | 1.19±0.04** |
| LH | 1.54±0.09** | 1.17±0.08** | 1.10±0.04** | 1.09±0.01** |
| MH | 2.30±0.10**## | 0.93±0.05**## | 0.80±0.05*## | 0.91±0.04**## |
| HH | 3.01±0.04*## | 0.62±0.05## | 0.55±0.08## | 0.53±0.02## |
| Positive drug | 2.44±0.21**## | 0.72±0.02## | 0.72±0.10## | 0.78±0.05**## |
表6 各组大鼠结肠组织c-Kit、CD47、p-PI3K/PI3K、p-Akt/Akt蛋白表达比较
Tab.6 Comparison of c-Kit, CD47, p-PI3K and p-Akt protein expressions in the colon tissue of the rats in each group (Mean±SD, n=3)
| Group | c-Kit/β-actin | CD47/β-actin | p-PI3K/PI3K | p-Akt/Akt |
|---|---|---|---|---|
| Control | 3.37±0.05 | 0.59±0.05 | 0.53±0.10 | 0.47±0.02 |
| Model | 1.24±0.14** | 1.26±0.07** | 1.24±0.02** | 1.19±0.04** |
| LH | 1.54±0.09** | 1.17±0.08** | 1.10±0.04** | 1.09±0.01** |
| MH | 2.30±0.10**## | 0.93±0.05**## | 0.80±0.05*## | 0.91±0.04**## |
| HH | 3.01±0.04*## | 0.62±0.05## | 0.55±0.08## | 0.53±0.02## |
| Positive drug | 2.44±0.21**## | 0.72±0.02## | 0.72±0.10## | 0.78±0.05**## |
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