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Pay attention to the "acid rebound" after the sudden stop of acid inhibitors-Polyprezinc will go further with you

Pay attention to the "acid rebound" after the sudden stop of acid inhibitors-Polyprezinc will go further with you

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

(Summary description)

Pay attention to the "acid rebound" after the sudden stop of acid inhibitors-Polyprezinc will go further with you

(Summary description)

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

  Preface

  When the gastric mucosa is pre-exposed to mild irritants or small doses of non-steroidal anti-inflammatory drugs (NSAIDs), the gastric mucosa will increase its resistance to them. Studies have shown that the endogenous effects caused by inhibiting gastric acid or increasing mucosal blood flow The increase of prostaglandin E2 (PGE2) helps gastric mucosal cells to adapt to stimulating drugs; on the other hand, it also shows the importance of heat shock protein as an endogenous cytoprotective agent. The endogenous cytoprotective factor 72-kDa heat shock protein (HSP72) can be induced by mild irritants, thereby protecting the gastric mucosa from various damaging drugs. When using acid inhibitors (PPI and H2RA) to treat ulcers, recurrence may occur after stopping the drug. This is likely to be due to the rebound of gastric acid secretion and aggravate gastric mucosal damage. So, is it necessary to appropriately extend the use of mucosal protective agent after acid suppression therapy? The study is as follows: Polyprezinc (a chelate composed of zinc ions and L-carnosine) is a mucosal protective agent, clinically It is commonly used to treat gastric ulcers. At the same time, it is also a recognized HSP72 inducer. In this study, we studied whether the expression of HSP72 in the gastric mucosa can be regulated by gastric acid. At the same time, we studied the effects of PPI and H2RA on the expression of HSP72; in addition, this study further evaluated the expression of HSP72, a zinc derivative-Polyprezinc. The influence of the gastric mucosa and the protective effect on the gastric mucosa.

  Materials and Method

  1.1 Animal

  Male SD rats, weighing 250-300g, eat and drink freely, are raised in an environment of 12h dark-light cycle, 22±2°C and humidity (55±5%).

  1.2 Drugs

  Omeprazole (proton pump inhibitor, PPI), famotidine (H2 receptor antagonist, H2RA), polyprezinc (a chelate of zinc and L-carnosine, gastric mucosal protector).

  1.3 The effect of gastric acid inhibitors on the expression of HSP72

  The rats were fasted for 24 hours before the experiment, and were given famotidine (50 mg/kg dissolved in 1 mL of distilled water) and omeprazole (30 mg/kg dissolved in 1 mL of 0.5% carboxymethyl cellulose) (control group) ), then continue to administer famotidine and omeprazole (n=4 at each time point), and sacrifice the rats at 6, 12, 24, 48, and 72 h. The protein concentration was determined by the Bradford method, and the grayscale of the immunostaining band was analyzed by scanning grayscale image analysis program. The relative grayscale value was calculated by the following formula. Relative gray (%) = gray (after administration)/gray (before PPI or H2RA administration) × 100.

  1.4 The effect of zinc derivatives on the expression of HSP72

  In order to evaluate the effect of polyprezinc (HSP72 inducer) on the low-level expression of HSP72 in the gastric mucosa, 6h (famotidine) and 42h (omeprazole) after the administration of acid inhibitors were given intragastric zinc sulfate and polyprezine. Rezine (100mg/kg).

  The protective effect of 0.6N HCl on gastric mucosa under the condition of low level of 1.5 HSP72

  12h (famotidine) and 48h (omeprazole) after administration of 1mL 0.6 N HCl, 6h later, the rats were sacrificed, the stomach was taken, the gastric mucosal damage was observed, the ulcer index was measured, and the gastric mucosal damage was evaluated severity.

  1.6 The effect of zinc derivative pre-induced HSP72 on the protective ability of gastric mucosa

  In order to evaluate the effect of gastric mucosa in inducing HSP72, 6 hours after administration of zinc derivatives, HCl continued to intervene in the treatment of famotidine and omeprazole. The control group, famotidine and omeprazole treatment groups were treated with HCl for 6 hours to compare the severity of injury (ulcer index) in each group.

  1.7 Determination of pH in the stomach

  In order to understand whether the pH value in the stomach contributes to mucosal damage and the expression of HSP72, the pH value in the stomach was measured every 1h to 6h after administration and 6, 12, 24, 48 and 72h after administration (each time point, n=4).

  1.8 Statistical analysis

  The results are expressed as mean ± standard deviation, and n is the number of rats. Statistical significance was evaluated using a two-tailed t test, and P<0.05 was significant.

  Results and analysis

  2.1 The influence of H2RA and PPI on the expression of HSP72

  Famotidine and omeprazole can significantly reduce the expression of HSP72 in the gastric mucosa of rats. The lowest expression level of HSP72 was observed at 12h after famotidine administration, and the expression level of HSP72 was observed at 48h after omeprazole administration. lowest.

  2.2 The effect of zinc derivatives on the expression of HSP72 in rats treated with acid suppression

  As shown in Figure 4, when famotidine was administered for 6 hours and omeprazole was administered for 42 hours, pretreatment with zinc derivatives significantly increased the expression of HSP72. In other words, before the acid suppressor caused the lowest level of HSP72, after pretreatment with zinc derivatives for 6 hours, the reduced HSP72 expression level increased significantly, and the effect of polyprezinc was stronger than zinc sulfate.

  2.3 HCl induces gastric mucosal damage

  Administer zinc derivatives before HCl pretreatment, the level of HSP72 increases, and it significantly inhibits gastric mucosal damage. The percentage of ulcer index of rats treated with famotidine plus zinc sulfate and polyprezinc were 17.2±7.9% and 11.7±7.0%, respectively. Similarly, the percentage of ulcer index in rats treated with omeprazole plus zinc sulfate and polyprezinc were 6.5±3.5% and 11.0±2.3%, respectively. Polyprezinc significantly increased HSP72 levels and prevented the stomach induced by 0.6NHCl Mucosal damage.

  2.4 The effect of intragastric pH on gastric mucosal injury and HSP72 expression

  As shown in Figure 6, the expression of HSP72 in the gastric mucosa decreased with acid suppression (increase in pH) caused by acid inhibitors. Under the condition of low levels of HSP72, HCl significantly inhibited the protective effect of gastric mucosa when invaded.

  As shown in Figure 7, under the condition of low levels of HSP72, the famotidine and omeprazole treatment group had more severe gastric mucosal damage when HCl invaded compared with the control group and the zinc treatment group, which induced the zinc derivative of HSP72 expression ——Polyprezinc can significantly inhibit gastric mucosal damage.

  Discuss

  "Studies have shown that the expression level of HSP72 in gastric mucosa is regulated by physiological gastric acid. When acid inhibitors such as PPI and H2RA are used, the expression of HSP72 decreases, indicating that gastric acid secretion may be an important physiological factor in gastric mucosa HSP72 regulation. Polyprezinc can significantly reverse the decrease in HSP72 expression induced by acid inhibitors and significantly increase the expression level of HSP72. At the same time, polyprezinc can significantly protect the gastric mucosal damage induced by 0.6N HCl under the condition of low HSP72 levels. Therefore, after the sudden discontinuation of acid-suppressive drugs in clinical treatment, it is necessary to appropriately extend the treatment course of the mucosal protective agent polyprezinc to reduce gastric acid rebound and mucosal damage caused by down-regulation of protective factors.

  Relaisheng (Polyprezinc Granules) increases the expression level of HSP72 and enables HSP72 to play its "molecular chaperone" function, thereby mediating the protective effect on endogenous cells of the gastric mucosa. For patients with ulcers, Relaisheng is an inhibitor The "best partner" of acid, Relaisen is safer, long-term use without accumulation, can accompany you to go further.

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Jilin Province Great Great Pharmaceutical Co. LTD
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