Shenmai Injection Upregulates Heme Oxygenase-1 to Confer Protection Against Severe Acute Pancreatitis

Fei-Hu Zhang; Yang Liu; Xiao-Bin Dong; Hao Hao; Kai-Liang Fan; Xian-Qing Meng; Li Kong

doi:10.1016/j.jss.2020.06.035

Shenmai Injection Upregulates Heme Oxygenase-1 to Confer Protection Against Severe Acute Pancreatitis

J Surg Res. 2020 Dec:256:295-302. doi: 10.1016/j.jss.2020.06.035. Epub 2020 Jul 23.

Authors

Fei-Hu Zhang¹, Yang Liu², Xiao-Bin Dong², Hao Hao², Kai-Liang Fan², Xian-Qing Meng², Li Kong²

Affiliations

¹ The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China; Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. Electronic address: zfh_1341@163.com.
² Department of Emergency Center, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.

PMID: 32712444
DOI: 10.1016/j.jss.2020.06.035

Abstract

Background: To explore the mechanism of Shenmai injection (SMI) on severe acute pancreatitis (SAP) through heme oxygenase-1 (HO-1) signaling.

Methods: A total of 40 male Sprague-Dawley (SD) rats (220-260 g) were grouped into the following four categories (n = 10): SAP + SMI + Zinc protoporphyrin (ZnPP), SAP + SMI, SAP, and sham surgery groups. ZnPP is a specific inhibitor of HO-1. Four percent of sodium taurocholate (1 mL/kg) was retrogradely injected via the pancreatic duct to induce the SAP model. The SAP group rats received 1.6 mL/kg saline by intravenous injection 30 min after the induction of SAP. The SAP + SMI group rats received 1.6 mL/kg SMI by intravenous injection 30 min after the induction of SAP. The SAP + SMI + ZnPP group rats received an intravenous injection of 1.6 mL/kg SMI and intraperitoneal administration of 30 mg/kg ZnPP 30 min after the SAP induction. Twenty-four hours after the SAP induction, blood samples were collected for the measurement of amylase, lipase, creatinine, myeloperoxidase, interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and HO-1 level, while tissue specimens were harvested for the determination of HO-1, TNF-α, and IL-10 mRNA level. Meanwhile, histopathological changes in organs (pancreas, lung, and kidney) were stored.

Results: The serum concentration of amylase, lipase, creatinine, and myeloperoxidase was higher in the SAP group than in the SAP + SMI group. Treatment with SMI increased HO-1 and IL-10 level and reduced TNF-α level in serum and tissues compared to the SAP group (P < 0.05). Treatment with SMI abolished the organ-damaging effects of SAP (P < 0.05). Furthermore, suppression of HO-1 expression by ZnPP canceled the aforementioned effects.

Conclusions: SMI confers protection against the SAP-induced systemic inflammatory response and multiple organs damage via HO-1 upregulation.

Keywords: Heme oxygenase-1; Inflammation; Organs; Severe acute pancreatitis; Shenmai injection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amylases / blood
Animals
Disease Models, Animal
Drug Combinations
Drugs, Chinese Herbal / administration & dosage*
Heme Oxygenase (Decyclizing) / metabolism*
Humans
Lipase / blood
Male
Pancreas / drug effects*
Pancreas / immunology
Pancreas / pathology
Pancreatitis / blood
Pancreatitis / complications
Pancreatitis / diagnosis
Pancreatitis / drug therapy*
Peroxidase / blood
Rats
Severity of Illness Index
Systemic Inflammatory Response Syndrome / blood
Systemic Inflammatory Response Syndrome / diagnosis
Systemic Inflammatory Response Syndrome / etiology
Systemic Inflammatory Response Syndrome / prevention & control*
Up-Regulation / drug effects

Substances

Drug Combinations
Drugs, Chinese Herbal
fructus schizandrae, radix ginseng, radix ophiopogonis drug combination
Peroxidase
Heme Oxygenase (Decyclizing)
Hmox1 protein, rat
Lipase
Amylases