Experimental Study On The Overexpression Of Detrusor Smooth Muscle Cell Connexin43 By Cyclic Stretch In Vitro

Backgroud and Objective: Detrusor instability (DI) is a frequent bladder dysfunction which affects intensively people's health. It can cause frequency, urgency, necessitous incontinence, and more severely, it can damage kidney and nephric duct. Although the incidence of DI is very frequent in clinic, its curative effect is unsatisfactory. The major reason is that the mechanism of DI is little known.The increase of intercellular communication is regarded as a significative reason to the development of DI. A major pathway for intercellular communication is via gap junctional channels, which are plasma strutures that form intercellular channels between adjacent cells. Through these channels,small molecules (MW<1000Da), such as ions, second messengers, Ca²⁺, cAMP and cGMP, can rapidly diffuse from cell to cell. The intercellular communication mediated by gap junction called gap junctional intercellular communication (GJIC), which is involved in many biologic process, such coordination of the contraction of uterus and smooth muscle cells, exchange of nutrients and ions between connected cells, transfer of electrical signals, control of cell growth and pathways for signaling compounds.Nowadays, over ten connexin (Cx) proteins have been found in bladder detrusor smooth muscle cell (DSMC), and Cx43 is the widest distributed in the condition of DI, which is found to increase mainly among these connexin proteins in obstructed bladder and instable detrusor. So the increase of Cx43 is of important significance in the development of DI. But the mechanisms of the Cx43 overexpression is little known.As described by many authors, detrusor instability frequently occurs because of bladder outlet obstruction. Structural changes lead to functional changes in the obstructed bladder. Urodynamic overload appears to be the underlying stimulus. It is clear from clinical pressure-flow studies that high-pressure voiding is consistently observed in patients with benign prostatic obstruction. Similar results were observed in rats with bladder outlet obstruction, showing that micturition pressure in obstructed bladders was significantly increased compared with controls. An increase in bladder wall tension (mechanical stretch...