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A new choice for the treatment of inflammatory bowel disease-Polyprezinc particles

A new choice for the treatment of inflammatory bowel disease-Polyprezinc particles

  • Categories:Stomach healthy
  • Author:
  • Origin:
  • Time of issue:2020-12-02
  • Views:0

(Summary description)

A new choice for the treatment of inflammatory bowel disease-Polyprezinc particles

(Summary description)

  • Categories:Stomach healthy
  • Author:
  • Origin:
  • Time of issue:2020-12-02
  • Views:0
Information

  Preface

  Heat shock proteins (HSPs) are highly conserved proteins expressed in eukaryotic and prokaryotic cells. It is believed that HSPs are important for cell growth and development. Studies have shown that various stresses such as heat, toxins and some heavy metals can induce the production of heat shock proteins, among which zinc ions can induce the production of heat shock proteins (HSPs). Heat shock proteins are divided into four families: HSP90, HSP70, HSP60 and low molecular weight HSP. In the colonic mucosa, the 72-kDa heat shock protein (HSP72), as a "molecular chaperone", plays an important role in cell protection. Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor. The transcription of many pro-inflammatory factors (TNF-α, IL-1β and IL-8) is regulated by NF-κB activation. Therefore, NF-κB Activation also plays a vital role in inflammation.

  Polyprezinc is a chelate composed of zinc ions and L-carnosine, and is often used clinically to treat gastric ulcers. Polyprezinc can effectively prevent gastric mucosal damage without affecting gastric acid secretion and endogenous prostaglandins. Its anti-ulcer effect is attributed to its membrane stability and antioxidant activity. This study mainly examined the effects of anti-ulcer drug polyprezinc on acetic acid-induced colonic mucosal injury, and the correlation between these effects and the activation of HSP72 and NF-κB in colonic mucosa.

  1 Materials and methods

  1.1 Animal

  Male SD rats (250-300 g) aged 15-20 weeks were reared in an environment with a temperature of 22±2°C and a humidity of 55±5% for a 12-hour cycle of dark-light.

  1.2 Western blot analysis of HSP72 expression in colonic mucosa

  Polyprezinc (30 mg/kg) before pretreatment and every 3h after administration, rats were sacrificed to 12h, colonic mucosa was taken, and stored at −80°C for later use. The colonic mucosa was homogenized with trichloro-ice buffer of pH=5.5, the homogenate was centrifuged at 18000×g for 20min, the supernatant was collected, and the protein concentration was adjusted to 0.2mg/mL, and the protein concentration was determined by Bradford method. The cell membrane was incubated with anti-HSP72 antibody and treated with horseradish peroxidase coupled with anti-rabbit IgG (1:1500). The gray scale of immunostained bands was analyzed with the NIH image program scanning gray scale. Use the formula to calculate the relative gray scale of the dyed zone: relative gray scale (%) = gray scale (after polyprezine administration)/gray scale (before polyprezine administration)×100.

  1.3 Electrophoretic mobility change analysis (EMSA)

  Rats were intrarectally administered polyprezinc (30 mg/kg), and the rats were sacrificed to 9 hours before and every 3 hours after the administration, and the colonic mucosa was taken. Electrophoretic mobility transfer analysis (EMSA) was used to detect the binding activity of NF-κB and its shared oligonucleotide in the nuclear extract of rat colonic mucosa.

  1.4 Acetic acid-induced colonic mucosal injury

  In order to study the effect of polyprezinc on acetic acid-induced colonic mucosal damage, rats were intrarectally administered polyprezinc, and 5% acetic acid 1.0mL was given intrarectally before administration and every 3h. The rats were sacrificed 24h after fasting with water. Take the colon, cut along the edge of the mesentery, and measure the area of ​​colonic mucosa injury. The lesion score is expressed as the total lesion area (mm²) of the colonic surface area.

  1.5 The effects of polyprezinc, zinc sulfate and L-carnosine on HSP72 expression and acetic acid-induced colonic mucosal injury

  In order to study the effects of the components of polyprezinc on HSP72 expression and acetic acid-induced colon injury, rats were intrarectally administered polyprezinc (30 mg/kg), zinc sulfate and L-carnosine. The rats were sacrificed 6h later. Western blotting was used to detect the expression of HSP72 in colonic mucosa.

  1.6 Data analysis

  All data are expressed as the mean ± SE of 4 independent experiments. Data analysis used one-way analysis of variance, using Student's test and Bonferoni's multiple comparison adjustment or Wilcoxon's rank sum test to analyze unpaired data.

  2 Results and analysis

  2.1 Polyprezinc increases HSP72 expression

  As shown in Figure 1, after polyprezinc pretreatment, the expression of HSP72 in the colonic mucosa of rats was significantly increased.

  After pretreatment with polyprezinc, the relative gray scale of HSP72 evaluated by gray measurement method and the relative gray scale at 0 h were 185.5±25.9% (3h; P<0.05) and 247.5±20.1% (6h; P< 0.001), 188±21.4% (9h; P<0.01), 156.5±35.0% (12h; NS).

  2.2 Polyprezinc inhibits NF-κB activity in colonic mucosa

  Compared with the control group, the NF-κB binding activity of colonic mucosa was significantly inhibited 6h after polyprezinc pretreatment.

  2.3 Polyprezinc treatment of acetic acid-induced colonic mucosal injury

  Macroscopic observation of polyprezinc on acetic acid-induced colonic mucosal injury (A): without pretreatment with polyprezinc; (B): pretreatment with polyprezinc 6h before acetic acid treatment. Polyprezinc pretreatment can significantly prevent acetic acid-induced mucosal ulcers and erosions.

  After polyprezinc pretreatment, compared with the non-administered group (357.7±19.1mm²/mouse), the lesion score was significantly reduced, 3h after polyprezine administration (202.6±31.5mm²/mouse, P<0.05), 6h (109.7±14.0mm²/piece, P<0.01), 9h (204.7±12.0mm²/piece, P<0.05), 12h (314.6±28.3mm²/piece, NS), at 6h, polyprezinc protects the intestinal mucosa The most significant effect.

  2.4 The effect of polyprezinc, zinc sulfate and L-carnosine on HSP72 expression and acetic acid-induced colonic mucosal injury

  After pretreatment with polyprezinc and zinc sulfate, the expression of HSP72 in colonic mucosa increased significantly, but L-carnosine did not increase the expression of HSP72. Compared with the zinc sulfate treatment group (P<0.01), the polyprezinc treatment group had a higher induction rate of HSP72 in the colonic mucosa, and zinc ions and carnosine had a synergistic effect.

  Polyprezinc and zinc sulfate pretreatment can significantly reduce the damage score, but L-carnosine cannot prevent acetic acid-induced colonic mucosal damage.

  Discuss

  "In summary, polyprezinc can promote the expression of "molecular chaperone" HSP72, inhibit the activity of inflammatory factor NF-κB, and effectively prevent and treat acetic acid-induced colonic mucosal injury. Boda Weiye Ruilaisheng (Polyprezinc Granules) protects colonic mucosal damage by inducing HSP72 expression and inhibiting NF-κB activity. It can be used as a new option for the treatment of inflammatory bowel disease and is widely used in clinical practice.

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