Polyprezinc up-regulates the expression of IGF-I mRNA (3)
- Categories:Stomach healthy
- Time of issue:2020-12-03
Polyprezinc up-regulates the expression of IGF-I mRNA (3)
- Categories:Stomach healthy
- Time of issue:2020-12-03
Diabetes mellitus (DM) is a disease caused by lack of insulin in the body, and is a risk factor for peptic ulcer in elderly patients. Diabetes has a negative impact on cell migration, proliferation, capillary growth, and granulation tissue metabolism, leading to a decline in wound repair ability. Some of these processes are regulated by polypeptide growth factors. Diabetes is a dysfunction that can be treated with insulin. Since the expression of insulin-like growth factor I (IGF-I) is greatly reduced in diabetic animals and human tissues, the formation of new blood vessels and collagen deposition are essential for gastric mucosal recovery. important. Studies have shown that the topical application of recombinant human insulin growth factor I (rhIGF-I) to skin wounds, gastric mucosal injuries and periodontal wounds of normal and diabetic animals can achieve a healing stimulating effect, which strongly supports the above statement. Zinc ion is an essential trace element for many metal enzymes to function. Among them, DNA and RNA polymerase are very important for tissue repair. Lack of zinc will delay the wound healing of pig skin and connective tissue, and L-carnosine accelerates wound healing and has immunomodulatory effects. Polyprezinc (Polaprezinc, PZ) is a chelate composed of zinc ions and L-carnosine, and the combination of the two aims to achieve a synergistic effect of enhancing ulcer healing. Studies have shown that polyprezinc can promote the expression of IGF-I in mesenchymal cells, which shows that IGF-I plays an important role in the repair of gastric epithelial cells. So what effect does diabetes have on gastric mucosal damage and repair? What effect does Polyprezinc have on the damaged gastric mucosa? Please see the following research.
Materials and Method
1.1 Animals and groups
200-220g male SD rats were randomly divided into control group, diabetes group and insulin treatment group, 5 weeks before the experiment, intraperitoneal injection of streptozotocin (STZ, 70mg/kg) induced diabetes. The control group received the same amount of normal saline. Measure the changes in tail vein blood glucose concentration (BGLs) and body weight. Rat blood glucose levels (BGLs) higher than 350mg/100mL are considered as diabetes. One week after STZ injection, animals were randomly selected to be treated with 4 IU/day/rat zinc insulin for 4 weeks.
1.2 Experimental method
Fasting for 18 hours before the experiment, and no water for 1 hour. 1 mL of 0.6N hydrochloric acid was injected into the stomach, and the rats were sacrificed at different time points (1, 3, 4, 5, 7 and 10 days). Pretreatment with polyprezinc (3-30 mg/kg, bid) for 4 days to study the effect of polyprezinc on the healing of gastric mucosal injuries. Pretreatment with ZnSO4·7H2O (29.6mg/kg), L-carnosine (23.3mg/kg) and a mixture of ZnSO4·7H2O and L-carnosine (29.6±23.3mg/kg), the dose is the same as 30mg/kg polyprezinc Similarly, compare the effects of polyprezinc and its components on gastric mucosal injury. RhIGF-I (10-200µg/kg, bid) was injected subcutaneously for 4 days to study the effect of rhIGF-I on gastric mucosal injury.
Blood samples are taken before dissection and hydrochloric acid treatment to detect the effects of drugs on blood glucose concentration and healing effects. Take the stomach, make an incision along the large curve, and place it under a dissecting microscope (X10) with a square grid to examine the injury site. Measure the area of the lesion (mm²) as the injury score.
1.3 Determination of acid secretion
Measure the gastric acid secretion ability of the rat's pyloric ligation stomach under basic conditions. Fasting for 18h before the experiment. The abdominal wall was incised under light ether anesthesia, and the pylorus was ligated. After ligating the pylorus for 4 hours, the rats were sacrificed with excessive ether and the stomach contents were collected. After 3000 revolutions/centre 15 min, the volume was measured. The results are expressed as titratable acidity, acid output and gastric juice volume. In addition, the effects of polyprezinc (30mg/kg, bid) and rhIGF-I (200μg/kg, bid) on the secretion of diabetic rat acid were also studied.
1.4 IGF-I gene expression
Detect the expression of IGF-I gene in rat gastric mucosa. A modified acid guanidine thiocyanate-phenol-chlorophenol method was used to extract total RNA from cells. RT-PCR and Southern hybridization were used to detect the IGF-I mRNA content. The ECL detection kit of horseradish peroxidase labeled with anti-FI antibody detects the signal on the x-ray film. X-ray film analysis was performed with a V10 image analyzer.
1.5 Statistical analysis
Appropriate use of one-way analysis of variance (ANOVA) and Bonferroni or Tukey-Kramer multiple comparison method or non-parametric Mann-Whitney determination method for statistical analysis, P<0.05 has a significant difference.
Results and analysis
2.1 Changes in rat body weight and blood glucose
Normal rats injected with saline increased their initial body weight, while diabetic rats lost 12.8% of their body weight within 4 weeks. Insulin significantly prevented the weight loss of rats. After injection of STZ, the BGLs of rats increased, reaching 3 times the baseline value at 1 week, and continued to increase after 4 weeks. Insulin can significantly reduce the blood sugar of diabetic mice, but its value is still higher than that of normal animals. There was no significant change in BGLs of rats in the control group.
2.2 HCl induces gastric mucosal damage in rats
In the control group and diabetic mice, 0.6N HCl (1 mL) intragastric administration induced severe hemorrhagic lesions. There was no significant difference in the lesion area between the two groups. The injury scores 1h after HCl administration were 210±25.5mm² and 205±24.7mm², respectively. Both groups were cured within 10 days, and the damage of the control group and diabetic rats decreased to 8.8% (18±6.6mm²) and 15.2% (31.2±11.5mm²) of the initial value, respectively. The damaged area is surrounded by granulation tissue and covered with a newly formed thin layer of epithelium. Diabetes can delay injury healing, and the injury score of diabetic rats at 3, 5, and 7 days after hydrochloric acid treatment is significantly higher than that of rats born in the same litter.
2.3 The effect of insulin on gastric mucosal injury in rats
Because the BGLs of STZ group rats were significantly increased, the effect of insulin on HCl-induced gastric injury in STZ diabetic rats was studied. One hour after the injection of hydrochloric acid, the effect of insulin on the development of gastric mucosal injury is not significant. The injury score is 225±15.1mm², which is equivalent to normal (210±25.5mm²) and untreated diabetic (205±24.7mm²) rats, but BGLs There are significant differences (Figures 1 and 2, Tables 1 and 2). On the other hand, insulin significantly improved the healing rate of gastric mucosal injury in STZ diabetic rats. Compared with the untreated diabetic rats with a gastric injury score of 95.9±9.1mm², this gastric injury score is 27.4±4.31mm². The healing process of the injury is accelerated and blood sugar is significantly reduced.
2.4 The effect of polyprezinc and its components on gastric mucosal injury in rats
Increasing the dose of polyprezinc (3-30 mg/kg, bid) has no effect on the hyperglycemia of STZ diabetic mice. After 4 days of treatment, the blood glucose level is still much higher than 350 mg/100 mL. However, polyprezinc has a dose-dependent opposite effect to the harmful effects of diabetes in the treatment of gastric injury. A significant difference has been observed at 10 mg/kg, with an injury score of 39.1±6.2mm², which is untreated diabetes 62.8% of rats.
To compare the effects of polyprezinc and its components, ZnSO4·7H2O, L-carnosine and a mixture of ZnSO4.7H2O and L-carnosine were pretreated with a dose equivalent to 30 mg/kg polyprezinc. The results showed that ZnSO4·7H2O and the mixture of ZnSO4·7H2O and L-carnosine did not have the effect of polyprezinc on the healing of gastric injury, and L-carnosine could not accelerate the healing of stomach injury in STZ diabetic rats.
2.5 Expression of IGF-I mRNA in gastric mucosa of rats
IGF-I gene expression was observed in the gastric mucosa of normal rats, but this expression was significantly reduced in the stomach of diabetic rats. Both insulin and polyprezinc can significantly promote IGF-I mRNA expression.
2.6 Gastric acid secretion in rats
Compared with normal animals, the gastric acid, gastric acid output, and gastric juice volume of diabetic rats were reduced by 53.8%, 64.8%, and 45.8%, respectively. Insulin could reverse the decline of these parameters, but polyprezinc did not affect the secretion of gastric acid in diabetic rats. Reduce any significant impact.
2.7 The effect of rhIGF-I on the healing of rat stomach injury
"RhIGF-I administered in increasing doses (10-200mg/kg, bid) will not affect the high BGLs of STZ diabetic mice. Even if the highest dose is used for 4 days, its value remains above 350mg/100 mL. However, rhIGF-I has a dose-dependent adverse effect on the harmful effects of diabetes in the treatment of gastric injury.
RhIGF-I (10µg/kg) can significantly reduce the gastric injury score (64.0±14.8mm²), which is 37.5% of untreated diabetic rats. Since the healing of gastric injury is adjusted by the acidity of the official cavity, we tested the effect of rhIGF-I on gastric acid secretion in normal rats. rhIGF-I (200µg/kg, bid) lasted for 4 days without affecting gastric acid secretion. The acid output reached 74.1±14.5µeq/hr (N=4), which was not significantly different from untreated rats (N=4; 61.4±7.7µeq/hr).
The expression of IGF-I mRNA in the diabetic gastric mucosa was significantly reduced, indicating that the synthesis of IGF-I in the diabetic gastric mucosa was damaged before transcription, which delayed the healing of acute gastric mucosal injury. Polyprezinc increases the level of IGF-I mRNA in the gastric mucosa and partially corrects the defects of IGF-I expression, thereby accelerating the healing of gastric mucosal injuries.
Boda Weiye Ruilaisheng (Polyprezinc Granules) is a mucosal protective agent with a unique mechanism of action. By up-regulating the expression of IGF-I mRNA, it speeds up gastric mucosal healing and effectively treats acute gastric mucosal injury.
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