Protective Effect of Shenfu Injection on Liver Injury Following Hind Limb Ischemia-Reperfusion_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 TANPing ¹ ,  ZHANGLing-yun ¹ , ZHANGGuo-xin ² , LIUYe-rong ¹ , HeYan-hong ¹ , LIUZhi-han ¹

1. Department of Anesthesiology, Traditional Chinese medical Hospital of Gansu Province, Lanzhou 730050, Gansu Province, China;
2. College of Pathology, Kunming medical University, Kunming 650031, Yunnan Province, China;

Corresponding author：

ZHANGLing-yun, Email: zhangly8848@126.com

Keywords：

Shenfu injection; Hind limb ischemia-reperfusion; Liver injury; Hemeoxygenase

DOI：

10.7507/1007-9424.20140232

Video：

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Objective To investigate the protective effect of Shenfu injection on liver injury in rats with hind limb ischemia-reperfusion and its mechanism. Methods Sixty-four male rats were randomly divided into sham operation group, ischemia-reperfusion group, Shenfu group〔Shenfu injection 7.5 mL/kg injection of peritoneal(ip), given 10 min before ischemia-reperfusion〕, Shenfu+Znpp group(Shenfu injection 7.5 mL/kg+Znpp 5 mg/kg ip, given 10 min before ischemia-reperfusion), 16 rats in each group. The rat model of hind limb ischemia-reperfusion injury was reproduced by occluding the hind limb artery of the rats for 3 h and subsequent reperfusing for 4 h. The liver tissues were gathered for malondialdehyde(MDA)and superoxide dismutase(SOD)determination. The expression of hemeoxygenase 1(HO-1)protein in the liver tissues was detected by immunohistochemistry. The pathological changes of liver were observed under the light microscope. The changes of serum glutamate-pyruvate transaminase(GPT)and glutamine oxaloacetic transaminase(GOT)were observed respectively. Results ①Compared with the sham operation group, the contents of MDA, GPT, GOT, and the expression of HO-1 protein were markedly increased in the ischemia-reperfusion group, Shenfu group, and Shenfu+Znpp group(P < 0.05), the activities of SOD were markedly decreased in the ischemia-reperfusion group and Shenfu+Znpp group(P < 0.05).②Compared with the ischemia-reperfusion group, the contents of MDA, serum GPT, GOT, and the expression of HO-1 protein were markedly decreased, the activity of SOD was markedly increased in the Shenfu group(P < 0.05).③Compared with the Shenfu group, the contents of MDA, GPT, GOT were markedly increased, the activity of SOD was markedly decreased in the Shenfu+Znpp group(P < 0.05). Unde ther light microscope, the pathological changes induced by ischemia-reperfusion were significantly attenuated by the Shenfu injection in the Shenfu group and were reversed by the Znpp in the Shenfu+Znpp group. Conclusion Shenfu injection inhibits liver tissue injury during hind limb ischemia-reperfusion, this protective effect might be partly through induction of HO-1.

Citation： TANPing, ZHANGLing-yun, ZHANGGuo-xin, LIUYe-rong, HeYan-hong, LIUZhi-han. Protective Effect of Shenfu Injection on Liver Injury Following Hind Limb Ischemia-Reperfusion. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(8): 960-964. doi: 10.7507/1007-9424.20140232 Copy

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2.	Iida H, Schmeichel AM, Wang Y, et al. Orchestration of the inflammatory response in ischemia-reperfusion injury[J]. J Peripher Nerv Syst, 2007, 12(2): 131-138.
3.	Yassin MM, Harkin DW, Barros D'Sa AA, et al. Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction[J]. World J Surg, 2002, 26(1): 115-121.
4.	Zhang Y, Leng YF, Xue X, et al. Effects of penehyclidine hydrochloride in small intestinal damage caused by limb ischemia-reperfusion[J]. World J Gastroenterol, 2011, 17(2): 254-259.
5.	Suzuki Y, Deitch EA, Mishima S, et al. Inducible nitric oxide synthase gene knockout mice have increased resistance to gut injury and bacterial translocation after an intestinal ischemia-reperfusion injury[J]. Crit Care Med, 2000, 28(11): 3692-3696.
6.	Souza Filho MV, Loiola RT, Rocha EL, et al. Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats[J]. Braz J Med Biol Res, 2009, 42(10): 921-929.
7.	Zheng CD, Min S. Cardioprotection of shenfu injection against myocardial ischemia/reperfusion injury in open heart surgery[J]. Chin J Integr Med, 2008, 14(1): 10-16.
8.	石臣磊, 秦华东, 丁超.依达拉奉对肝缺血再灌注损伤逆转作用的研究[J].中国普外基础与临床杂志, 2011, 18(8): 887-889.
9.	贺泽龙, 袁卫红, 邹晓玲.参附注射液对充血性心力衰竭患者血流动力学的影响及机理探讨[J].中国中西医结合杂志, 2001, 21(5): 386-387.
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11.	郑曙云, 徐建国, 赵振中.参附注射液对大鼠心肌缺血再灌注损伤的影响[J].中国中西医结合杂志, 2004, 24(6): 541-544, 548.
12.	殷文朋, 李春盛.参附注射液对心源性休克犬血流动力学及氧代谢的影响[J].中国中西医结合急救杂志, 2008, 15(1): 20-23.
13.	杨芳炬, 郑有顺, 李东晓, 等.参附注射液的微循环作用研究[J].生物医学工程学杂志, 2003, 20(1): 91-94, 100.
14.	Hassoun HT, Kozar RA, Kone BC, et al. Intraischemic hypothermia differentially modulates oxidative stress proteins during mesenteric ischemia/reperfusion[J]. Surgery, 2002, 132(2): 369-376.
15.	Harkin DW, Barros D'Sa AA, Yassin MM, et al. Recombinant bactericidal/permeability-increasing protein attenuates the systemic inflammatory response syndrome in lower limb ischemia-reperfusion injury[J]. J Vasc Surg, 2001, 33(4): 840-846.
16.	Ben-Ari Z, Issan Y, Katz Y, et al. Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury[J]. Apoptosis, 2013, 18(5): 547-555.
17.	Tu YP, Chen SC, Liu YH, et al. Postconditioning with far-infrared irradiation increases heme oxygenase-1 expression and protects against ischemia/reperfusion injury in rat testis[J]. Life Sci, 2013, 92(1): 35-41.
18.	Sasaki T, Yoshida K, Kondo H, et al. Heme oxygenase-1 accelerates protumoral effects of nitric oxide in cancer cells[J]. Virchows Arch, 2005, 446(5): 525-531.
19.	Kuboki S, Schuster R, Blanchard J, et al. Role of heat shock protein 70 in hepatic ischemia-reperfusion injury in mice[J]. Am J Physiol Gastrointest Liver Physiol, 2007, 292(4): G1141-G1149.
20.	Wang Y, Shen J, Xiong X, et al. Remote ischemic preconditioning protects against liver ischemia-reperfusion injury via heme oxygenase-1-induced autophagy[J]. PLoS One, 2014, 9(6): e98834.

1. Bonheur JA, Albadawi H, Patton GM, et al. A noninvasive murine model of hind limb ischemia-reperfusion injury[J]. J Surg Res, 2004, 116(1): 55-63.
2. Iida H, Schmeichel AM, Wang Y, et al. Orchestration of the inflammatory response in ischemia-reperfusion injury[J]. J Peripher Nerv Syst, 2007, 12(2): 131-138.
3. Yassin MM, Harkin DW, Barros D'Sa AA, et al. Lower limb ischemia-reperfusion injury triggers a systemic inflammatory response and multiple organ dysfunction[J]. World J Surg, 2002, 26(1): 115-121.
4. Zhang Y, Leng YF, Xue X, et al. Effects of penehyclidine hydrochloride in small intestinal damage caused by limb ischemia-reperfusion[J]. World J Gastroenterol, 2011, 17(2): 254-259.
5. Suzuki Y, Deitch EA, Mishima S, et al. Inducible nitric oxide synthase gene knockout mice have increased resistance to gut injury and bacterial translocation after an intestinal ischemia-reperfusion injury[J]. Crit Care Med, 2000, 28(11): 3692-3696.
6. Souza Filho MV, Loiola RT, Rocha EL, et al. Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats[J]. Braz J Med Biol Res, 2009, 42(10): 921-929.
7. Zheng CD, Min S. Cardioprotection of shenfu injection against myocardial ischemia/reperfusion injury in open heart surgery[J]. Chin J Integr Med, 2008, 14(1): 10-16.
8. 石臣磊, 秦华东, 丁超.依达拉奉对肝缺血再灌注损伤逆转作用的研究[J].中国普外基础与临床杂志, 2011, 18(8): 887-889.
9. 贺泽龙, 袁卫红, 邹晓玲.参附注射液对充血性心力衰竭患者血流动力学的影响及机理探讨[J].中国中西医结合杂志, 2001, 21(5): 386-387.
10. 戴晓明, 冯振卿, 吴慧平, 等.参附注射液对大鼠肾缺血再灌注损伤作用的影响[J].南京中医药大学学报, 1998, 14(2): 84-85.
11. 郑曙云, 徐建国, 赵振中.参附注射液对大鼠心肌缺血再灌注损伤的影响[J].中国中西医结合杂志, 2004, 24(6): 541-544, 548.
12. 殷文朋, 李春盛.参附注射液对心源性休克犬血流动力学及氧代谢的影响[J].中国中西医结合急救杂志, 2008, 15(1): 20-23.
13. 杨芳炬, 郑有顺, 李东晓, 等.参附注射液的微循环作用研究[J].生物医学工程学杂志, 2003, 20(1): 91-94, 100.
14. Hassoun HT, Kozar RA, Kone BC, et al. Intraischemic hypothermia differentially modulates oxidative stress proteins during mesenteric ischemia/reperfusion[J]. Surgery, 2002, 132(2): 369-376.
15. Harkin DW, Barros D'Sa AA, Yassin MM, et al. Recombinant bactericidal/permeability-increasing protein attenuates the systemic inflammatory response syndrome in lower limb ischemia-reperfusion injury[J]. J Vasc Surg, 2001, 33(4): 840-846.
16. Ben-Ari Z, Issan Y, Katz Y, et al. Induction of heme oxygenase-1 protects mouse liver from apoptotic ischemia/reperfusion injury[J]. Apoptosis, 2013, 18(5): 547-555.
17. Tu YP, Chen SC, Liu YH, et al. Postconditioning with far-infrared irradiation increases heme oxygenase-1 expression and protects against ischemia/reperfusion injury in rat testis[J]. Life Sci, 2013, 92(1): 35-41.
18. Sasaki T, Yoshida K, Kondo H, et al. Heme oxygenase-1 accelerates protumoral effects of nitric oxide in cancer cells[J]. Virchows Arch, 2005, 446(5): 525-531.
19. Kuboki S, Schuster R, Blanchard J, et al. Role of heat shock protein 70 in hepatic ischemia-reperfusion injury in mice[J]. Am J Physiol Gastrointest Liver Physiol, 2007, 292(4): G1141-G1149.
20. Wang Y, Shen J, Xiong X, et al. Remote ischemic preconditioning protects against liver ischemia-reperfusion injury via heme oxygenase-1-induced autophagy[J]. PLoS One, 2014, 9(6): e98834.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective Effect of Shenfu Injection on Liver Injury Following Hind Limb Ischemia-Reperfusion

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