Dataset Information

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

ABSTRACT:

Background

Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model.

Materials and methods

Forty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair's scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-? (TNF-?) and transforming growth factor-? (TGF-?). The collagen deposition was assessed by Sirius red staining and ?-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H₂O₂ and DHI, and NF-?B phosphorylation was detected to illustrate the effect of DHI on oxidative stress.

Results

The intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-?, TGF-?1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-?B phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs.

Conclusion

DHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.

SUBMITTER: Wu Y

PROVIDER: S-EPMC6721271 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

Wu Yunhua Y Wei Guangbing G Yu Junhui J Chen Zilu Z Xu Zhengshui Z Shen Rui R Liang Ting T Zheng Lu L Wang Kang K Sun Xuejun X Li Xuqi X

Oxidative medicine and cellular longevity 20190819

<h4>Background</h4>Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model.<h4>Materials and methods</h4>Fo ...[more]

PMID: 31531183

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Project description:Background/aimDanhong injection (DHI) is a Chinese patent drug used for relieving cardiovascular diseases. Recent studies have suggested that DNA methylation plays a pivotal role in the maintenance of cardiac fibrosis (CF) in cardiovascular diseases. This study was aimed at identifying the effect and the underlying mechanism of DHI on CF, especially the DNA methylation.MethodsA CF murine model was established by thoracic aortic constriction (TAC). A 28-day daily treatment with or without DHI via intraperitoneal injection was carried out immediately following TAC surgery. The changes in cardiac function, pathology, and fibrosis following TAC were measured by echocardiography and immunostaining. We used methyl-seq analysis to assess the DNA methylation changes in whole genes and identified the methylation changes of two Ras signaling-related genes in TAC mice, including Ras protein activator like-1 (Rasal1) and Ras-association domain family 1 (Rassf1). Next, the methylation status and expression levels of Rasal1 and Rassf1 genes were consolidated by bisulfite sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting, respectively. To determine the underlying molecular mechanism, the expressions of DNA methyltransferases (DNMTs), Tet methylcytosine dioxygenase 3 (TET3), fibrosis-related genes, and the activity of Ras/ERK were measured by RT-qPCR and Western blotting.ResultsDHI treatment alleviated CF and significantly improved cardiac function on day 28 of TAC. The methyl-seq analysis identified 42,606 differential methylated sites (DMSs), including 19,618 hypermethylated DMSs and 22,988 hypomethylated DMSs between TAC and sham-operated mice. The enrichment analysis of these DMSs suggested that the methylated regulation of Ras signal transduction and focal adhesion-related genes would be involved in the TAC-induced CF development. The results of bisulfite sequencing revealed that the TAC-induced methylation affected the CpG site in both of Rasal1 and Rassf1 genes, and DHI treatment remarkably downregulated the promoter methylation of Rasal1 and Rassf1 in CF hearts. Furthermore, DHI treatment upregulated the expressions of Rasal1 and Rassf1, inhibited the hyperactivity of Ras/ERK, and decreased the expressions of fibrosis-related genes. Notably, we found that DHI treatment markedly downregulated the expression of DNMT3B in CF hearts, while it did not affect the expressions of DNMT1, DNMT3A, and TET3.ConclusionAberrant DNA methylation of Rasal1 and Rassf1 genes was involved in the CF development. DHI treatment alleviated CF, prevented the hypermethylation of Rasal1 and Rassf1, and downregulated DNMT3B expression in CF hearts.

Project description:Stroke is the second most common cause of death worldwide. A systematic description and characterization of the strokes and the effects induced in the hippocampus have not been performed so far. Here, we analysed the protein expression in the hippocampus 24 h after cerebral ischaemic injury and repair. Drug intervention using Danhong injection (DHI), which has been reported to have good therapeutic effects in a clinical setting, was selected for our study of cerebral ischaemia repair in rat models. A larger proteome dataset and total 4091 unique proteins were confidently identified in three biological replicates by combining tissue extraction for rat hippocampus and LC-MS/MS analysis. A label-free approach was then used to quantify the differences among the four experimental groups (Naive, Sham, middle cerebral artery occlusion (MCAO) and MCAO + DHI groups) and showed that about 2500 proteins on average were quantified in each of the experiment group. Bioinformatics analysis revealed that in total 280 unique proteins identified above were differentially expressed (P < 0.05). By combining the subcellular localization, hierarchical clustering and pathway information with the results from injury and repair phase, 12 significant expressed proteins were chosen and verified with respect to their potential as candidates for cerebral ischaemic injury by Western blot. The primary three signalling pathways of the candidates related may be involved in molecular mechanisms related to cerebral ischaemic injury. In addition, a glycogen synthase kinase-3β (Gsk-3β) inhibitor of the candidates with the best corresponding expression trends between western blotting (WB) and label-free quantitative results were chosen for further validation. The results of Western blot analysis of protein expression and 2,3,5- chloride three phenyl tetrazole (TTC) staining of rat brains showed that DHI treatment and Gsk-3β inhibitor are both able to confer protection against ischaemic injury in rat MCAO model. The observations of the present study provide a novel understanding regarding the regulatory mechanism of cerebral ischaemic injury.

Project description:ImportanceAdhesion-related complications (ARCs), including small-bowel obstruction, are common complications of intra-abdominal surgery. Statins, which have antifibrotic pleiotropic effects, inhibit adhesion formation in murine models but have not been assessed in humans.ObjectiveTo assess whether statin use at the time of intra-abdominal surgery is associated with a reduction in ARCs.Design, setting, and participantsThese 2 separate retrospective cohort studies (The Health Improvement Network [THIN] and Optum's Clinformatics Data Mart [Optum]) compared adults receiving statins with those not receiving statins at the time of intra-abdominal surgery. Individuals undergoing intra-abdominal surgery from January 1, 1996, to December 31, 2013, in the United Kingdom and from January 1, 2000, to December 31, 2016, in the US were included in the study. Those with obstructive events before surgery or a history of inflammatory bowel disease were excluded. Data analysis was performed from September 1, 2012, to November 24, 2020.ExposureThe primary exposure was statin use at the time of surgery.Main outcomes and measuresThe primary outcome was ARCs, defined as small-bowel obstruction or need for adhesiolysis, occurring after surgery. Sensitivity analyses included statin use preceding but not concurrent with surgery, fibrate use, and angiotensin-converting enzyme inhibitor use. All analyses were adjusted for age, sex, and conditions associated with microvascular disease, such as hypertension, hyperlipidemia, obesity, and tobacco use; surgical approach and site; and diagnosis of a malignant tumor.ResultsA total of 148 601 individuals met the inclusion criteria for THIN (mean [SD] age, 49.6 [17.7] years; 70.1% female) and 1 188 217 for Optum (mean [SD] age, 48.2 [16.4] years; 72.6% female). A total of 2060 participants (1.4%) experienced an ARC in THIN and 54 136 (4.6%) in Optum. Statin use at the time of surgery was associated with decreased risk of ARCs (THIN: adjusted hazard ratio [HR], 0.81; 95% CI, 0.71-0.92; Optum: adjusted HR, 0.92; 95% CI, 0.90-0.95). Similar associations were appreciated between statins and small-bowel obstruction (THIN: adjusted HR, 0.80; 95% CI, 0.70-0.92; Optum: adjusted HR, 0.88; 95% CI, 0.85-0.91).Conclusions and relevanceThis study's findings suggest that, among individuals in 2 separate cohorts undergoing intra-abdominal surgery, statin use may be associated with a reduced risk of postoperative ARCs. Statins may represent an inexpensive, well-tolerated pharmacologic option for preventing ARCs.

Dataset Information

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

Background

Materials and methods

Results

Conclusion

Publications

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

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