Effect of bone marrow mesenchymal stem cells via portal vein injection on transforming growth factor-βR1 and -βR2 in rats with acute liver failure_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Tubing ¹ , LI Li ² , MU Hanzheng ² ,  LUO Xingdi ² , SHUAI Ling ³ , ZHANG Yujun ³

1. Department of General Surgery, The Sixteenth Hospital of PLA, Aletai, Xinjiang Uygur Autonomous Region 836500, P.R.China;
2. Medical Affair, The Sixteenth Hospital of PLA, Aletai, Xinjiang Uygur Autonomous Region 836500, P.R.China;
3. Institute of Hepatobiliary Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R.China;

Corresponding?author：

LUO Xingdi, Email: 750711050@qq.com

Keywords：

bone marrow mesenchymal stem cell; transforming growth factor-β receptor 1; transforming growth factor-β receptor 2; acute liver failure; rat

DOI：

10.7507/1007-9424.201612081

Video：

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Objective To investigate effect of bone marrow mesenchymal stem cells (BMSCs) via portal vein injection on transforming growth factor-β receptor 1 (TGF-βR1) and TGF-βR2 in rats with acute liver failure (ALF). Methods Sixty male SD rats were randomly divided into a normal control group, ALF model group, and BMSCs treatment group, with 20 rats in each group. The rats of normal control group were directly sacrificed without other treatment. The ALF models were made in the rats of BMSCs treatment group and ALF model group, then were treated with BMSCs and equal volume of normal saline respectively. On day 7 after treatment, the 1-week survival situation of rats was observed, the pathological change was observed by HE staining, the apoptosis of liver cells was detected by TUNEL method, and the TGF-βR1 and TGF-βR2 proteins expressions were detected by Western blot method. Results ① The 1-week survival rate of the BMSCs treatment group was significantly higher than that of the ALF model group (P<0.05). ② In the ALF model group, the liver cells were diffuse necrosis, the lobular structure was indistinct, and a large number of bridging necrosis. In the BMSCs treatment group, the infiltrations of inflammatory cells were decreased, and the structure of hepatic lobules gradually recovered, and the normal hepatocytes were seen around it. ③ The apoptosis indexes of the BMSCs treatment group and the ALF model group were significantly higher than those in the normal control group (P<0.05), which in the BMSCs treatment group was significantly lower than that of the ALF model group (P<0.05). ④ The TGF-βR1 and TGF-βR2 proteins expressions in the liver tissues of the ALF model group were significantly higher than those of the normal control group (P<0.05), which of the BMSCs treatment group were significantly lower than those of the ALF model group (P<0.05). Conclusion BMSCs could inhibit apoptosis of hepatocytes in ALF. Its mechanism might be related to expressions of TGF-βR1 and TGF-βR1 proteins, but its specific regulatory pathway needs to be further studied.

Citation： XU Tubing, LI Li, MU Hanzheng, LUO Xingdi, SHUAI Ling, ZHANG Yujun. Effect of bone marrow mesenchymal stem cells via portal vein injection on transforming growth factor-βR1 and -βR2 in rats with acute liver failure. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(8): 953-957. doi: 10.7507/1007-9424.201612081 Copy

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2.	Karvellas CJ, Todd Stravitz R, Battenhouse H, et al. Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transpl, 2015, 21(1): 4-12.
3.	Butterworth RF. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. J Clin Exp Hepatol, 2015, 5(Suppl 1): S96-S103.
4.	Romero-Gómez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol, 2015, 62(2): 437-447.
5.	王香梅. 拉米夫定與恩替卡韋治療慢性乙型肝炎慢加亞急性肝衰竭的臨床研究. 中國臨床研究, 2014, 27(3): 297-298.
6.	郭會敏, 李穎, 朱彥濤, 等. 36 例人工肝膽紅素吸附治療肝衰竭病人的護理. 護理研究, 2015, 29(7): 2423-2424.
7.	張美華, 余衛, 王巧瑜, 等. 骨髓間充質干細胞治療大鼠白毒傘中毒致急性肝衰竭的效果. 廣東醫學, 2016, 37(13): 1917-1920.
8.	Robles-Diaz M, Lucena MI, Kaplowitz N, et al. Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology, 2014, 147(1): 109-118. e5.
9.	Karkhanis J, Verna EC, Chang MS, et al. Steroid use in acute liver failure. Hepatology, 2014, 59(2): 612-621.
10.	Li H, Xia Q, Zeng B, et al. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol, 2015, 63(1): 50-59.
11.	Feng T, Zhang J, Zeng G, et al. Therapeutic potential of umbilical cord mesenchymal stem cells in mice with acute hepatic failure. Int J Artif Organs, 2015, 38(5): 271-276.
12.	李小鵬, 張倫理. 慢加急性肝衰竭研究新進展. 內科急危重癥雜志, 2014, 20(3): 157-158.
13.	李曉東. HBV 相關慢加急性肝衰竭免疫病理發病機制研究進展. 實用肝臟病雜志, 2015, 18(3): 317-320.
14.	劉海霞, 朱躍科, 孟慶華. 慢加急性肝衰竭的定義、病理生理學基礎和臨床管理. 臨床肝膽病雜志, 2016, 32(9): 1684-1687.
15.	賈琳, 李娟, 朱躍科, 等. 乙型肝炎相關慢加急性肝衰竭患者外周血樹突狀細胞水平及臨床意義. 臨床肝膽病雜志, 2015, 31(5): 711-715.
16.	盧新軍, 陳穎華, 馬毅, 等. 原位肝移植術后耐激素性急性排斥反應的臨床診治策略. 中華肝臟病雜志, 2016, 24(4): 297-301.
17.	白建華, 陳剛, 朱新鋒, 等. 原位肝移植模型的建立技巧與改進. 中國組織工程研究, 2015, 19(40): 6526-6530.
18.	吳婧, 倪鎏達. 急性肝衰竭預后評估模型的研究近況. 肝臟, 2015, 24(3): 248-250.
19.	裴利娟, 徐鴻濱, 金鑫, 等. 急性肝功能衰竭急診肝移植圍術期治療的單中心經驗探討. 中國組織工程研究, 2014, 18(36): 5741-5746.
20.	崔麗娜, 韓英. 多能干細胞在肝臟損傷和修復過程中的免疫調節作用. 臨床肝膽病雜志, 2014, 30(9): 855-859.
21.	宋囡, 何文智, 王智民, 等. 骨髓間充質干細胞在骨向分化的作用及中醫藥研究進展. 中國骨質疏松雜志, 2014, 20(1): 95-99.
22.	李志超, 楊海杰, 劇飛, 等. TGF-β1 通過激活 Smad 信號途徑抑制 PI3K/AKT 信號介導的 BMSC 成脂分化. 中國生物化學與分子生物學報, 2015, 31(10): 1077-1084.
23.	鄭盛, 楊涓, 張帆, 等. 骨髓間充質干細胞移植對急性肝功能衰竭大鼠血清及肝組織 HMGB1 表達的影響. 中華器官移植雜志, 2015, 36(12): 714-719.
24.	王海燕, 何創, 肖建斌, 等. 轉化生長因子-β-1 抗體對肺損傷纖維化大鼠細胞外基質重建紊亂的調控. 醫學研究生學報, 2014, 24(4): 368-372.
25.	符培亮, 叢銳軍, 張雷, 等. 體外條件下 TGF-β3、BMP-2 和 DEX 誘導兔滑膜間充質干細胞向軟骨細胞譜系分化的研究. 中國骨與關節雜志, 2014, 13(2): 135-141.
26.	靳艷文, 葉輝, 熊先澤, 等. PPARγ 激動劑拮抗 TGF-β1 介導的膽管纖維化的初步研究. 中國普外基礎與臨床雜志, 2016, 23(7): 790-793.
27.	曲心宇, 胡孝海, 劉君, 等. 血清 TGF-β1 和 IL-23 在胃癌診斷中的臨床應用價值. 中國普外基礎與臨床雜志, 2016, 23(7): 818-821.

1. Bajaj JS, O’Leary JG, Reddy KR, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology, 2014, 60(1): 250-256.
2. Karvellas CJ, Todd Stravitz R, Battenhouse H, et al. Therapeutic hypothermia in acute liver failure: a multicenter retrospective cohort analysis. Liver Transpl, 2015, 21(1): 4-12.
3. Butterworth RF. Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure. J Clin Exp Hepatol, 2015, 5(Suppl 1): S96-S103.
4. Romero-Gómez M, Montagnese S, Jalan R. Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure. J Hepatol, 2015, 62(2): 437-447.
5. 王香梅. 拉米夫定與恩替卡韋治療慢性乙型肝炎慢加亞急性肝衰竭的臨床研究. 中國臨床研究, 2014, 27(3): 297-298.
6. 郭會敏, 李穎, 朱彥濤, 等. 36 例人工肝膽紅素吸附治療肝衰竭病人的護理. 護理研究, 2015, 29(7): 2423-2424.
7. 張美華, 余衛, 王巧瑜, 等. 骨髓間充質干細胞治療大鼠白毒傘中毒致急性肝衰竭的效果. 廣東醫學, 2016, 37(13): 1917-1920.
8. Robles-Diaz M, Lucena MI, Kaplowitz N, et al. Use of Hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury. Gastroenterology, 2014, 147(1): 109-118. e5.
9. Karkhanis J, Verna EC, Chang MS, et al. Steroid use in acute liver failure. Hepatology, 2014, 59(2): 612-621.
10. Li H, Xia Q, Zeng B, et al. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation. J Hepatol, 2015, 63(1): 50-59.
11. Feng T, Zhang J, Zeng G, et al. Therapeutic potential of umbilical cord mesenchymal stem cells in mice with acute hepatic failure. Int J Artif Organs, 2015, 38(5): 271-276.
12. 李小鵬, 張倫理. 慢加急性肝衰竭研究新進展. 內科急危重癥雜志, 2014, 20(3): 157-158.
13. 李曉東. HBV 相關慢加急性肝衰竭免疫病理發病機制研究進展. 實用肝臟病雜志, 2015, 18(3): 317-320.
14. 劉海霞, 朱躍科, 孟慶華. 慢加急性肝衰竭的定義、病理生理學基礎和臨床管理. 臨床肝膽病雜志, 2016, 32(9): 1684-1687.
15. 賈琳, 李娟, 朱躍科, 等. 乙型肝炎相關慢加急性肝衰竭患者外周血樹突狀細胞水平及臨床意義. 臨床肝膽病雜志, 2015, 31(5): 711-715.
16. 盧新軍, 陳穎華, 馬毅, 等. 原位肝移植術后耐激素性急性排斥反應的臨床診治策略. 中華肝臟病雜志, 2016, 24(4): 297-301.
17. 白建華, 陳剛, 朱新鋒, 等. 原位肝移植模型的建立技巧與改進. 中國組織工程研究, 2015, 19(40): 6526-6530.
18. 吳婧, 倪鎏達. 急性肝衰竭預后評估模型的研究近況. 肝臟, 2015, 24(3): 248-250.
19. 裴利娟, 徐鴻濱, 金鑫, 等. 急性肝功能衰竭急診肝移植圍術期治療的單中心經驗探討. 中國組織工程研究, 2014, 18(36): 5741-5746.
20. 崔麗娜, 韓英. 多能干細胞在肝臟損傷和修復過程中的免疫調節作用. 臨床肝膽病雜志, 2014, 30(9): 855-859.
21. 宋囡, 何文智, 王智民, 等. 骨髓間充質干細胞在骨向分化的作用及中醫藥研究進展. 中國骨質疏松雜志, 2014, 20(1): 95-99.
22. 李志超, 楊海杰, 劇飛, 等. TGF-β1 通過激活 Smad 信號途徑抑制 PI3K/AKT 信號介導的 BMSC 成脂分化. 中國生物化學與分子生物學報, 2015, 31(10): 1077-1084.
23. 鄭盛, 楊涓, 張帆, 等. 骨髓間充質干細胞移植對急性肝功能衰竭大鼠血清及肝組織 HMGB1 表達的影響. 中華器官移植雜志, 2015, 36(12): 714-719.
24. 王海燕, 何創, 肖建斌, 等. 轉化生長因子-β-1 抗體對肺損傷纖維化大鼠細胞外基質重建紊亂的調控. 醫學研究生學報, 2014, 24(4): 368-372.
25. 符培亮, 叢銳軍, 張雷, 等. 體外條件下 TGF-β3、BMP-2 和 DEX 誘導兔滑膜間充質干細胞向軟骨細胞譜系分化的研究. 中國骨與關節雜志, 2014, 13(2): 135-141.
26. 靳艷文, 葉輝, 熊先澤, 等. PPARγ 激動劑拮抗 TGF-β1 介導的膽管纖維化的初步研究. 中國普外基礎與臨床雜志, 2016, 23(7): 790-793.
27. 曲心宇, 胡孝海, 劉君, 等. 血清 TGF-β1 和 IL-23 在胃癌診斷中的臨床應用價值. 中國普外基礎與臨床雜志, 2016, 23(7): 818-821.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of bone marrow mesenchymal stem cells via portal vein injection on transforming growth factor-βR1 and -βR2 in rats with acute liver failure

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