Application of mir-146a-5p to treating visceral hypersensitivity of irritable bowel syndrome
A technology of 1. mir-146a-5p, mir-146a-5pagomir, applied in the medical field, can solve the problems of intestinal permeability serotonin signaling pathway and abnormal visceral or somatic hypersensitivity, etc. effect of visceral hypersensitivity
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[0028] Visceral hypersensitivity refers to the increased sensitivity and responsiveness of visceral tissue to various mechanical and chemical stimuli, including visceral hyperalgesia and allodynia, and the volume and pressure thresholds of the colorectum are significantly reduced during dilation stimulation. At present, the mechanism of visceral hypersensitivity in IBS has not been fully elucidated, which may include increased sensitivity of visceral receptors, abnormal sensory afferents, and increased excitability of central visceral sensory neurons. Low-grade inflammation is also involved in the formation of visceral hypersensitivity in IBS.
[0029] Agomirs are specially labeled and chemically modified double-stranded small RNAs that modulate the biological functions of target genes by mimicking endogenous miRNAs.
[0030] In order to make the above-mentioned and other objects, features and advantages of the present invention more obvious and easy to understand, the preferr...
Embodiment 1
[0031] Example 1 Detection of serum mir-146a-5p expression in patients with irritable bowel syndrome
[0032]The included research subjects included 5 patients with irritable bowel syndrome (IBS) who were treated in the Department of Gastroenterology, Qilu Hospital of Shandong University (with high visceral hypersensitivity), and 5 healthy volunteers were included in the healthy control group. The diagnostic criteria of diarrhea-predominant irritable bowel syndrome refer to Rome III diagnostic criteria. Exclusion criteria were: patients with other diseases causing diarrhea (tumor, thyroid disease, celiac disease, etc.); patients with a history of abdominal surgery or alarm symptoms (anemia, gastrointestinal bleeding, significant weight loss, abdominal mass); patients with coagulation Abnormal function or serious organic disease affecting heart, liver, kidney function; pregnant or breastfeeding. 3ml of venous blood from 10 subjects was drawn into a coagulation tube, left stand...
Embodiment 2
[0034] Example 2 Establishment of a mouse model of irritable bowel syndrome and agomir intervention
[0035] The mice were fasted for 24 hours, and the mice were anesthetized by intraperitoneal injection of 1% pentobarbital (0.2ml / mice). The anal tube was inserted into the anus of the mouse, and TNBS (80mg / kg) was injected into the anus about 5cm away from the anus. A model was established, and the blank control group was given an equal volume of normal saline for enema. After the enema, the mice were inverted for about 30 minutes to prevent the liquid from flowing out. The Agomir intervention method was to start hsa-mir-146a-5p agomir (3nmol / a) enema seven days after TNBS modeling, and enema every three days. The disease model control group and blank control group were given equal volume of normal saline enema. On the 28th day, colonic dilatation test was performed to evaluate visceral hypersensitivity, and then the mice were sacrificed to collect colonic tissue for follow-up...
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