What role do HSPs play in gastritis and ulcers?
- Categories:Stomach healthy
- Time of issue:2020-12-03
What role do HSPs play in gastritis and ulcers?
- Categories:Stomach healthy
- Time of issue:2020-12-03
With the discovery of gastric acid and pepsin in the stomach, people questioned the following questions: "Why doesn't the stomach digest itself?", "How does the stomach maintain its integrity under continuous exposure to secreted lysate?" and "Stomach How to resist Helicobacter pylori (Hp) infection and how to resist gastric mucosal damage caused by continuous non-steroidal anti-inflammatory drugs (NSAID)?"
The discovery of "gastric mucosal barrier" and "defense system" gave the answer.
"The first level gastric mucosal barrier includes factors secreted into the lumen, including bicarbonate, mucus, immunoglobulin, other antibacterial substances (lactoferrin) and surface active phospholipids.
The second-level defense system is gastric epithelial cells, which have significant resistance to acids and irritants, and can form a relatively weak passive diffusion barrier. In addition, if the continuity of epithelial cells is destroyed, it can quickly repair and recover.
The third gastric mucosal barrier is the mucosal microcirculation system, which is coordinated with sensory afferent nerves in the mucosa and submucosa. The back diffusion of acid or toxin to the mucosa leads to the increase of calcitonin gene-related peptide mediated by the nervous system, which helps to enhance the mucosal blood flow, which is very critical for preventing damage and promoting repair.
The fourth level of defense system is the mucosal immune system, which is composed of mast cells and macrophages. They regulate the inflammatory response in response to attacks and effectively protect the gastric mucosa.
In recent years, it is believed that heat shock proteins (HSPs) are another important factor for the gastric defense mechanism at the intracellular level. Some HSPs are expressed under non-stress conditions to maintain the integrity of normal cells. HSPs promote cell recovery by renaturating partially damaged functional proteins or increasing the delivery of precursor proteins to important organelles such as mitochondria and endoplasmic reticulum, thereby completing an effective mucosal defense mechanism and achieving the purpose of ulcer healing. Protect key enzymes related to cell protection. So what role do HSPs play in gastritis and ulcer healing?
Unbalanced aggressive and defensive factors determine the degree of gastric injury. The gastric mucosa is constantly attacked by various endogenous and exogenous stimulating factors, including gastric acid and pepsin, ethanol, active oxygen, and non-steroidal anti-inflammatory Drugs (NSAIDs), excessive mental stress, and Helicobacter pylori (Hp) infection (Figure 1A).
In order to protect the gastric mucosa from harmful factors, the stomach itself forms a complex defense system, including stimulating mucus production and bicarbonate, regulating gastric mucosal blood flow, accelerating epithelial cell regeneration and maintaining epithelial homeostasis. Among them, prostaglandin (PG ), especially PGE2, enhances these protective mechanisms, so PGE2 is considered to be the main factor of the gastric mucosal defense system. Like PGs, heat shock proteins (HSPs) are also an important protective mechanism.
Heat shock proteins (HSPs) were first discovered in 1962. Their expression is induced by heat shock and various other stresses. HSPs come in many forms and are classified into families according to their molecular weight. According to HSP90, HSP70, HSP60 and HSP27, HSP10 The biological activity and apparent molecular weight of small molecule HSPs are divided into four categories. When HSP60, HPS70, and HSP90 are constitutively expressed, HSP70 and HSP27 are induced by various conditions, including heat, oxidative stress, or drug exposure. Studies have shown that most HSPs have strong cytoprotective effects, participate in many regulatory pathways, and act as molecular chaperones to preserve important cellular proteins. Therefore, HSPs are essential for maintaining the integrity of gastric mucosal cells during normal cell growth and participating in various pathophysiological processes.
Hp infectious gastritis
Helicobacter pylori (Hp) infection leads to inflammation of the gastric mucosa, which is an important cause of gastritis and peptic ulcer disease, and is closely related to the occurrence and development of mucosal associated lymphoma (MALT) lymphoma and gastric cancer. Hp has a high urease activity, which leads to the production of large amounts of ammonia and causes an oxidative burst of neutrophils. Hp activates neutrophils to reduce O2 to superoxide (O2¯), and the disproportionation of O2¯ produces more hydrogen peroxide (H2O2) reactive free radicals. H2O2 myeloperoxidase catalyzes the oxidation of chloride to form hypochlorous acid (HOCl). HOCl reacts with ammonium (NH4﹢) to form monochloramine (NH2Cl), which is a stable lipophilic oxidant that easily penetrates the target cell membrane. Compared with H2O2 and HOCl, it is more cytotoxic to the gastric mucosa. Studies have shown that NH2Cl can cause severe gastric mucosal damage. Hp-related inflammation is characterized by severe infiltration of neutrophils and monocytes in the gastric mucosa. Therefore, the accumulation and activation of these inflammatory cells are related to the massive production of inflammatory cytokines and the generated reactive oxygen free radicals. Hp﹢ The patient's mucosal IL-1β, IL-6, IL-8 and TNF-α levels are higher.
"In addition to these destructive conditions, the reduction of HSP70 expression is also a factor that leads to gastritis and epithelial cell damage. As shown in Figures 2A and 2B, Hp infection caused a decrease in the expression of HSP70, which could not be detected after 4 hours. For the low expression of HSP70 associated with Hp infection, a reasonable explanation should be to inhibit HSF activation and reduce HSF-HSE complex formation. Therefore, the dysregulation of HSP70 expression may be the main cause of Hp-related mucosal damage, and induction of HSP70 expression may become a new method to prevent and treat the disease.
In some prospective studies, it has been found that Hp infection and psychological stress have a synergistic relationship with the formation of gastric ulcer. The recurrence rate of peptic ulcer in patients with Hp infection is much higher than that in patients with Hp eradication. Hp infection increases the risk of stress mucosal injury.
"In order to verify the significance of HSPs-induced Hp infection, HSP90, HSP70, HSP60 and HSP27 were tracked according to Hp infection alone and Hp infection during heat shock. In this case, the expression of HSP70 and HSP27 was significantly reduced, but HSP induced by heat shock, although infected with Hp, can still maintain HSP levels (Figure 3A). GGA is a drug for the treatment of gastric ulcer and gastritis. It is an HSP70 inducer. Although Hp infection, gastric cells after pretreatment still retain HSP70. Based on these results, the induction of HSP has nothing to do with the form, and HSP is resistant to iNOS and COX-2 (the main damage factors after Hp infection). In short, even under the over-attack of Hp, by inducing the expression of HSPs can alleviate the mucosal damage caused by stress.
In the presence of Hp infection, water immersion suppression stress (WIRS) was used for in vivo animal experiments. After applying WIRS, the expressions of HSP70, HSP60 and HSP27 were all significantly reduced, but supplementation with tocopherol can prevent WIRS-induced gastric mucosal damage by inducing HSP27 expression
Alcohol is one of the main causes of gastric mucosal damage, including gastritis and ulcers, which can develop into gastric ulcers. Alcohol-induced gastric mucosal injury can be directly or indirectly mediated and regulated by a variety of cellular molecules in the pathophysiology, such as cyclooxygenase, lipoxygenase, cytokines, cytochrome P450 2E1, thromboxane and oxygen free radicals derived free radicals Wait. Studies have shown that in the study of inducing HSP70 expression, the short-term survival rate of mice attacked by ethanol and endotoxin increased by 2 times, and the long-term survival rate increased by 5 times. HSP70 inducers can protect rats from alcohol-induced gastric mucosal damage, and induce large amounts of HSP70 to inactivate ethanol.
Other gastrointestinal injury
"Studies have shown that the induction of HSP70 expression in ethanol-pretreated cells has an adaptive cytoprotective effect on indomethacin-induced gastric mucosal damage, indicating that when NSAIDs inhibit PGE2 levels, HSP70 plays an important role in gastric mucosal adaptation.
Ruilaisheng (Polyprezinc Granules)-a chelate composed of zinc ions and L-carnosine, which is widely used clinically to treat gastric ulcers. Among them, zinc ion is an essential trace element for many enzymes in different biological systems. Among zinc-dependent enzymes, DNA and RNA polymerase play a vital role in the tissue repair process. They affect cell proliferation and protein synthesis. Zinc deficiency can delay the healing process of skin wounds and block the repair path of gastric ulcer healing. L-carnosine is the most ideal transporter for zinc, and the combination of the two produces a synergistic mucosal protective effect. The protective effect of polyprezinc on mucosa is mainly attributed to its stimulation of mucus secretion, antioxidant activity, membrane stabilization and induction of HSP70 expression. Not only that, Polyprezinc can accurately snipe the important pathogenic factor urease of Hp infection, thereby significantly improving the eradication rate of Hp. At the same time, its protective effect does not depend on dmPGE2, and it is a safe and effective mucosa that is non-toxic and does not accumulate. Protective agent.
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