Investigation on the Mechanism of Salvia miltiorrhiza in the Treatment of Postoperative Abdominal Adhesion Based on Network Pharmacology and Molecular Docking / 中国药房

OBJECTIVE：To investigate the potential mechanism of Salvia miltiorrhiza in the treatment of postoperative abdominal adhesion （PAA）. METHODS ：Active components and target genes of S. miltiorrhiza were retrieved from TCMSP database，SwissADME database ，Perl database ，UniProt database and other databases. GeneCards ，OMIM and PubMed database were used to retrieve target genes related to PAA. Venn diagram was drawn by using mapping tool of bioinformatic online database so as to screen the intersecting targets of active component-PAA. STRING platform was adopted to establish target network related to active component-PAA and protein-protein interaction （PPI）network of intersecting targets ，etc.，and to screen hub genes. Gene ontology（GO）and Kyoto Encyclopedia of Genes and Genom es（KEGG）pathway enrichment were carried out by using R 3.6.1 software. Using the protein encoded by hub gene as receptor and tanshinone Ⅱ A as ligand ，the molecular docking was carried out with AutoDock 1.5.6 tool. RESULTS ：A total of 38 active components of S. miltiorrhiza with high gastrointestinal absorption and their corresponding 72 targets，755 PAA-related target genes were identified. Results of Venn diagram showed that there were 33 intersecting targets of active components of chuqi90@163.com S. miltiorrhiza with PAA. Tanshinone ⅡA，dihydrotanshinolac- tone and other components may be important nodes of the target network related to active component-PAA. FOS，APP，ACHE， CASP3 and PTGS2 may be the hub genes in PPI network of intersecting targets. Results of GO enrichment showed that the intersecting targets were mainly concentrated in adrenergic receptor activity ，catecholamine binding ，G protein-coupled amine receptor activity and so on ；KEGG pathway enrichment analysis showed that the intersecting targets were mainly enriched in neuroactive ligand-receptor interaction ，cGMP-PKG signaling pathway ，endocrine resistance ，EGFR-tyrosine kinase inhibitor resistance and calcium signaling pathway.Molecular docking analysis showed that tanshinone ⅡA could form hydrogen bonds with many amino acid residues such as VAL- 580 of proto oncogenes c-Fos ，amyloid precursor protein ，acetylcholinesterase，caspase 3 and prostaglandin G/H synthase 2. CONCLUSIONS ：The active components of S. miltiorrhiza play a role in the treatment of PAA by directly or indirectly acting on neuroactive ligand-receptor interaction ，cGMP-PKG signaling pathway ，endocrine resistance ， EGFR-tyrosine kinase inhibitor resistance resistance and calcium signaling pathway.

Clinical study on treatment of severe retroperitoneal infection under "frozen abdomen" status / 中国中西医结合急救杂志

Objective To investigate the therapeutic method of extensive abdominal adhesion and organ edema ("frozen abdomen" status) with severe retroperitoneal infection. Methods The treatment measures, therapeutic course and characteristics of 21 patients with retroperitoneal infection complicated with sepsis under "frozen abdomen" status admitted to Rizhao Hospital of Traditional Chinese Medicine from 2004 to 2017 were retrospectively analyzed, inductive therapeutic measure and characteristics and the clinical efficacy and prognosis were also observed. Results In 21 cases, 19 cases were cured clinically, 1 case died of massive hemorrhage and 1 case died of multiple organ failure (MOF). In the 8 cases, abdominal cavity opening were performed, no exposure of intestinal fistula occurred, although the abdominal wall hernias were left behind in 6 cases and pancreatic pseudo-cyst was formed in 1 case. The patients total time of hospitalization was (61.0±10.5) days, and the stay in Intensive Care Unit (ICU) was (28±5) days. Conclusion In the comprehensive treatments, the multi-form flushing drainages were the core of effective means to control the severe retroperitoneal infection.

Prevention of abdominal adhesions in rats by rhynchophylline through inhibition of Smad singnaling pathway / 药学学报

Postoperative intra-abdominal adhesion is one of the most common complications in the postoperative period. Current remedies are very ineffective to prevent the pathological outcomes except steroid hormones. Rhynchophylline is deemed as a pharmacologically active component from traditional Oriental medicine Uncaria rhynchophylla (Miq.) Jacks. (Rubiaceae). This study was designed to investigate the preventative effect of rhynchophylline on the abdominal adhesions in rats. Rhynchophylline relieved the experimental abdominal adhesion and decreased the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the blood serum in a dose-dependent manner. The levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were reduced significantly in the peritoneal fluid. The potential mechanism of the activity is related to inhibition of the TGF-β1/Smad signaling pathway.

Progress on anti-adhesion therapy following gynecological laparoscopy / 中国内镜杂志

High incidence of postoperative abdominal adhesions after gynecological laparoscopy, which may induce a line of serious complications such as chronic pelvic soreness, intestinal obstruction, infertility, etc, has been clinically encountered with the major problems unsolved thus far. By further upgrading the merits of gynecological laparoscopy, including the small operative scope, mild injury and fine manipulation, coupled with the application of anti-adhesion therapies, reduced post-operative adhesions and improved clinical outcomes can be expected. Research has been actively persisted on this area in recent years to achieve new progress, especially in the development of anti-adhesion materials, as well as their clinical application and evaluation of the effects, which is overviewed in this review.

Inhibitory effect of electro-acunpunture at Zusanli point on flammatory factors of postoperative intra-abdominal adhesions / 军事医学

Objective To observe the inhibitive effect of electro-acupuncture (EA)at Zusanli points (ST36)on inflammatory mediators of postoperative intra-abdominal adhesions and study the relationship between EA and cholinergic anti-inflammatory pathway.Methods Forty-eight male Wistar rats were divided into 6 groups (each =8):Group A (control),Group B(abdominal adhesions model),Group C (abdominal adhesions plus EA),Group D(sham acu-point control),Group E (abdominal adhesions plus α-bungarotoxin )and Group F (abdominal adhesions plus EA after α-bungarotoxin).Animal models of abdominal adhesion were produced by Chiang’s path.Bilateral Zusanli points (ST36) and shame acupoints were electro-acupunctured at a constant voltage for 1 hour while rats were awake.The ɑ-BGT(1 μg/kg)was injected into the abdominal cavity after surgery.All the rats were sacrificed on the 3rd day,and the levels of inflammatory mediators (TNF-ɑ,NO and NOS)in tissues were evaluated.Results Three days after surgery,the damaged cecum of abdominal adhesion groups developed obvious edema that did not adhere with other tissues.Compared with sham control,the abdominal adhesion resulted in significant elevation of inflammatory mediators (TNF-ɑ,NO and NOS).EA at Zusanli points obviously lowered the elevated levels of inflammatory mediators (P <0.01 and P <0.05).EA at Zusanli points following the injection of ɑ-BGT showed less anti-inflammatory effect(P <0.01).Conclusion EA at Zusanli points significantly lowers the elevated levels of inflammatory mediators after abdominal adhesion challenge.The activation of cholinergic anti-inflammatory pathway might be one of the mechanisms by which Zusanli points exert anti-inflammatory effects.

Effect of ankaferd blood stopper in experimental peritoneal adhesion model

PURPOSE: Ankaferd Blood Stopper (ABS) is an herbal extract attained from 5 different plants. It has the therapeutic potential to be used for the management of external hemorrhage and controlling gastrointestinal bleedings. To date, the safety of ABS for intraperitoneal usage is not clear. In this study, we investigated the effectiveness and safety of using intraperitoneal ABS in an experimental peritoneal adhesion model. METHODS: Twenty-four male Wistar Albino rats were used in the study. The rats were randomly divided into 3 groups: saline, ABS, and control. On the 10th day, all rats were euthanized. The adhesions were evaluated by Nair's macroscopic adhesion classification, and pathologically evaluated with Zühlke's microscopic adhesion classification. RESULTS: macroscopic and microscopic comparison between the ABS and saline groups did not show any differences but both the ABS and saline groups were superior when compared to the control group. CONCLUSION: ABS was found equally effective with saline on the abdominal adhesions and to no effect on postoperative adhesion formation.

Efficacy of vitamin E and selenium for the prevention of intra-abdominal adhesions in rats: uterine horn models

OBJECTIVE: This study compares the efficacies of vitamin E and selenium, both individually and in combination, for the prevention of postoperative intra-abdominal adhesions in rats. METHODS: Forty-seven female rats were divided into five groups. The sham animals (S group, n = 7) were given only laparotomies and intraperitoneally received 0.9 percent NaCl (2 ml). In the 40 other rats, abrasions of the left uterine horn were performed, followed by intraperitoneal administration of either 2 ml 0.9 percent NaCl (C group), 10 mg vitamin E (vitamin E group), 0.2 mg/kg selenium (Se group) or 10 mg vitamin E with 0.2 mg/kg selenium (vitamin E + Se group), with 10 animals in each treatment group. RESULTS: Adhesion formation was significantly reduced in animals in the Se and vitamin E + Se groups (p<0.05). Tissue catalase and glutathione peroxidase activities did not significantly differ between the groups. However, catalase and glutathione peroxidase activities and reduced glutathione levels were slightly increased in the vitamin E, Se and vitamin E + Se groups. In the vitamin E group, malondialdehyde concentrations were significantly lower than in the C group (p<0.05), but no significant differences were present among the S, C, Se and vitamin E + Se groups. Levels of nitric oxide were significantly higher in the C group than in the other groups (p<0.01). CONCLUSION: Intraperitoneal administration of selenium or combined vitamin E and selenium appears to be effective in preventing intra-abdominal adhesion formation in rat models through the reduction of lipid peroxidation products.

Study on preventive effect of volatile oil extracted from Foeniculum vulgare Mill. Seeds on postoperative intra-abdominal adhesions / 国际中医中药杂志

Objective To study the preventive effect of volatile oil extracted from Foeniculum vulgare Mill. Seeds on the formation of postoperative intra-abdominal adhesion. Methods Thirty-eihgt SD rats were randomly divided into sham operation group (10), operation group (14) and volatile oil treated group (14):sham operation group was only operated by abdominal incision, the rest two groups were established animal model of abdominal adhesion by rubbing the procussus vermiformis of cecum with dry sterile gauze, clamping and scuffing abdominal wall. Half of rats were separately killed on day 7 and day 14 after surgery, respectively.The degree of adhesion was evaluated according to Phillips 5-scale grade and the feature of this model. Results The scores of intra-abdominal adhesion were significantly lower in the carbachol group than those in operation group both on 7 d and 14 d(P＜0.01 ). Conclusion Volatile oil extracted from Foeniculum vulgare Mill. Seeds may take a significant role in the prevention of postoperative abdominal adhesion in rats.

Selective COX-2 inhibitor Celecoxib prevents postoperative abdominal adhesion / 西安交通大学学报(医学版)

Objective To determine the preventive effect of Celecoxib on postoperative adhesion formation and its mechanism. Methods We divided 80 SD rats into 5 groups: Groups A, B, C, H and S. Rats in Groups A, B, C and H received the operation of peritoneum rubbing to promote adhesion formation. Group S underwent sham operation. Rats in Group B were given Celecoxib of 40 mg/(kg·d), those in Group C were also given Celecoxib of 20mg/(kg·d), and those in Group H were given sodium hyaluronate (HA) during the operation. On the 8th and 15th postoperative day, half of the rats were sacrificed, the extent of adhesion formation was assessed and the adhesive peritoneum was subjected to immunohistochemistry with VEGF and CD_(34). Results The extent of postoperative adhesion differed significantly among the five groups (P<0.01). Groups B and C had significantly fewer adhesions than Groups H and A. VEGF was expressed most highly in Group A, followed by Groups H, C and B, and most weakly in Group S. CD34 was expressed most highly in Group A, followed by Groups H, C and B, and most weakly in Group S. Conclusion Celecoxib provides durable inhibition of intra-abdominal adhesions in a murine model compared with HA. The mechanism of preventing intra-abdominal adhesion via inhibiting COX-2 is possibly through down-regulated expression of VEGF and reduced microvascular density.

Prevention of abdominal adhesion with polyclonal antibody of transforming-growth factor beta : an experimental study / 中国普通外科杂志

Objective To block the bio function of TGF ? by the application of anti TGF ? polyclonal antibody, and observe its efficacy of prevention of abdominal adhesion. Methods The postoperative abdominal adhesion model was established in SD rats. The drugs were administrated by abdominal injection with saline (control group), sodium hyaluronate( HA group), and varied dosage of anti TGF? (anti TGF? groups) respectively. The adhesion was scored 21days later, while 30 of them were executed on the day 3 and day 10 after operation respectively. The expression of TGF ? was checked by immunohistochemistry in the samples obtained from the adhesion sites. Results The score of adhesion in anti TGF ? group (2.4?0.99) was significantly lower than that in control group (6.0?1.25) and HA group (3.4?1.03); in different dosage of anti TGF, the 50?g group showed its economical efficacy; in the control and HA groups the expression of TGF ? had a time dependent manner, which reachs to maximum in the day 3, and could be reduced by antibody. Conclusions The polyclonal antibody of TGF ? shows the power to prevent the postoperative abdominal adhesion in animal model, the mechanism of which is due to inhibition of TGF ? expression.