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Polyprezinc, a new way to protect the gastric mucosa-induce HO-1 production

Polyprezinc, a new way to protect the gastric mucosa-induce HO-1 production

  • Categories:Stomach healthy
  • Author:
  • Origin:
  • Time of issue:2020-12-03
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(Summary description)

Polyprezinc, a new way to protect the gastric mucosa-induce HO-1 production

(Summary description)

  • Categories:Stomach healthy
  • Author:
  • Origin:
  • Time of issue:2020-12-03
  • Views:0
Information

  Heme oxygenase (HO)-1 is involved in the cytoprotection of various organs. HO-1 is an induced isomer of HO. It catalyzes the degradation of heme to produce biliverdin, carbon monoxide (CO) and free iron. Then biliverdin is converted into bilirubin under the action of biliverdin reductase, free iron is quickly sequestered into ferritin, and CO causes vasodilation and inhibits platelet aggregation. In addition, bilirubin has high endogenous antioxidant activity. The adsorption of free iron by ferritin reduces the pro-oxidative state of cells. HO-1-dependent iron release will also up-regulate ferritin, thus inducing HO- The production of 1 can provide cell protection from oxidative stress. Polyprezinc is a chelate composed of zinc and carnosine. It is clinically used to treat gastric ulcers. It is a mucosal protective agent with both protective and repairing effects. Such protective effects can be attributed to the stimulation of mucus secretion and antioxidant activity. , Membrane stabilization and heat shock protein (HSP) 70 induction. According to reports, in addition to HSP70, HSP32 (considered HO-1) is also associated with gastrointestinal diseases. Therefore, we want to explore the possibility of polyprezinc inducing HO-1 and HSP70. If it can induce the production of HO-1, will it benefit from HCl-induced acute gastric mucosal injury?

  Materials and Method

  1.1 Tissue preparation

  Wistar male rats, 5 weeks old. Rats were sacrificed by intragastric administration of polyprezinc (50, 100 and 200 mg/kg) for 3 hours (n=5), and tissue samples were taken from the stomach; in the second experiment, rats were intragastrically administered with polyprezinc (200 mg/kg). kg) were sacrificed at 1h, 2h, 3h, 4h, 6h, 12h, 24h and 36h respectively (n=5), and tissue samples were taken from the stomach.

  1.2 Evaluation of gastric mucosal lesions

  Cut the stomach along the greater curvature of the stomach to expose the gastric mucosa, and record the appearance of the gastric mucosa with a digital camera. Use anatomical drawing and tracking software to evaluate mucosal lesions. Calculate the total surface area of ​​the mucous membrane damage area.

  1.3 SnMP pharmacological treatment

  Tin mesoporphyrin (SnMP) is a kind of HO-1 inhibitor. The vehicle (n=10) and SnMP (20μM/kg, n= 10) Pretreatment. Group A (PZ-, SnMP-, n=5): vehicle pretreatment, 60 minutes later, gavage with vehicle again; group B (PZ+, SnMP-, n=5): vehicle pretreatment, 60 min after gavage Prezinc (PZ); group C (PZ-, SnMP+, n=5): tin mesoporphyrin (SnMP) pretreatment, 60 minutes later, gavage vehicle again; group D (PZ+, SnMP+, n=5): Tin mesoporphyrin (SnMP) was pretreated, and polyprezinc (PZ) was intragastrically administered 60 minutes later. After 6h, each rat was given 0.6N HCl (0.4mL/100g) by intragastric administration, and then sacrificed 2h later, and a gastric specimen was taken.

  1.4 Real-time RT-PCR

  To extract total RNA from gastric tissue, real-time reverse transcriptase (RT) polymerase chain reaction (PCR) to detect the expression of HO-1 and HSP70 genes.

  1.5 Western Blot

  Determine the target protein level by plotting the relative standard curve of band density and β-actin band density.

  1.6 In situ hybridization (ISH)

  Slice in a cryostat, thawed and fixed on a silane-coated glass slide. The slides were coated with 1:2 diluted K-5 emulsion for automatic radiography, and then exposed at 4°C for 6-10 weeks. The slides were developed in D-19, and the sections were counterstained with hematoxylin-eosin for morphological examination.

  1.7 Apoptosis

  TUNEL staining and active caspase-3 immunostaining were used to detect the number of apoptotic cells and judge the degree of apoptosis.

  1.8 Data analysis

  uses one-way analysis of variance, Fisher's protected least significant difference test or Student't test for statistical analysis.

  Results and analysis

  2.1 Polyprezinc promotes the expression of HO-1 mRNA and HSP70 mRNA in rats

  After polyprezinc treatment, the level of HO-1 mRNA in rats increased in a dose-dependent manner. 200mg/kg polyprezinc increased by 9 times compared with the control group; compared with the control group, the HO-1 mRNA level increased significantly at 1 hour High, the maximum increase of 3-4 times in 2-3h, then gradually decreased, and the control level was restored within 6h; compared with the control group, HSP70 mRNA level also increased by 2-3 times in 2-3h.

  2.2 Gene mapping

  ISH showed that at 3h, HO-1 mRNA signal was strongly expressed on mucosal surface cells, and moderately expressed in scattered cells in the lamina propria and surrounding submucosa, but it was not detected in the control group. HSP70 mRNA signals are strongly expressed on the scattered cells and spindle cells of the mucosal surface cells, lamina propria and muscularis mucosa. These signals were not observed in the control group.

  2.3 Polyprezinc promotes immunoreactive HO-1 expression

  Western blotting showed that the immune response signal of HO-1 gradually increased, reaching 3 times the control level in 3-6h. The elevated level was maintained for 24h. There was no immune response to HO-1 and HSP70 in the control group. After 6h, clear HO-1 and HSP70 immunoreactive cells were observed on the corresponding cells, as shown by ISH. The lack of primary antibodies completely eliminated immunoreactivity (not shown). Double fluorescence immunohistochemistry showed that the HO-1 immunoreactive cells in the lamina propria and surrounding submucosa were ED1 positive, indicating that they were macrophages. Double fluorescence immunohistochemistry also showed that the HSP70 immunoreactive cells in the mucosal muscle layer were positive for α-smooth muscle cells, indicating that they were smooth muscle cells.

  2.4 Polyprezinc effectively protects the acute gastric mucosal injury induced by HCl

  After 2 hours of administration, blood clots and linear hemorrhage appeared on the damaged mucosal surface (AGML: Acute Gastric Mucosal Injury). The damage index of group B was significantly lower than that of group A, indicating that polyprezinc pretreatment can prevent HCl-induced AGML. The injury index of group C was significantly higher than that of group A, indicating that pretreatment with HO-1 inhibitor SnMP inhibited endogenous HO-1 activity and aggravated HCl-induced AGML. The damage index of group D was significantly lower than that of group C, indicating that although SnMP inhibited the endogenous and polyprezinc-induced HO-1 activity, polyprezinc effectively prevented HCl-induced AGML. The disease index of group D was not significantly higher than that of group B. However, the inhibition rate of group D was significantly lower than that of group B, indicating that polyprezinc-induced HO-1 is part of the mucosal protective effect of polyprezinc.

  2.5 Polyprezinc significantly inhibits HCl-induced mucosal cell apoptosis

  TUNEL staining and active caspase-3 immunostaining observed apoptotic cells on the damaged mucosal surface. The number of TUNEL positive cells was basically the same as the disease index. However, the number of apoptotic cells in group B seems to be less than that in group A, indicating that polyprezinc can prevent HCl-induced mucosal cell apoptosis. The number of apoptotic cells in group C was significantly higher than that in group A, indicating that pretreatment with HO-1 inhibitor SnMP to inhibit endogenous HO-1 activity increased HCl-induced mucosal cell apoptosis. The number of apoptotic cells in group D was significantly lower than that in group C, indicating that although SnMP inhibited the endogenous and polyprezinc-induced HO-1 activity, polyprezinc effectively prevented HCl-induced mucosal cell apoptosis.

  Discuss

  Studies have shown that polyprezinc can significantly promote the expression of HO-1 mRNA and HSP70 mRNA. At the same time, polyprezinc treatment effectively protects the acute gastric mucosal injury caused by HCl, and the induced HO-1 is also involved in this Kind of protection.

  Boda Weiye Ruilaisheng (Polyprezinc Granules) is an effective anti-oxidative response kinase inducer, which induces the production of HO-1, thereby providing cytoprotection against oxidative stress. It is a mucosal protective agent with a unique mechanism of action.

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